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Functionalization of resorcinarenes and study of antimicrobial activity

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Functionalization of resorcinarenes and study of antimicrobial activity
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English
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Muppalla, Kirankirti
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University of South Florida
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NMR
Crystal structure
Antimicrobial activity
Cavitand
Ring closing metathesis
Resorcinarene
Dissertations, Academic -- Chemistry -- Masters -- USF   ( lcsh )
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bibliography   ( marcgt )
theses   ( marcgt )
non-fiction   ( marcgt )

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Abstract:
ABSTRACT: Cavitands are very important class of compounds in supramolecular chemistry. These molecules contain rigid enforced cavity,and have attracted considerable attention in supramolecular chemistry as building blocks for the construction of carcerands, hemicarcerands, and other host guests complexes. Nearly 40 years ago, Niederl and Vogel laid foundation for the study of such type of condensation reactions. In our laboratory we are involved in synthesis of resorcinarenes with readily available substrates such as resorcinol and aldehydes to form a cyclic tetramer. Herein, I present detailed studies about the functionalization of the synthesized tetramers and their antimicrobial activity. Octahydroxy resorcinarenes were synthesized and perallylated which served as acyclic diene precursors for ring closing metathesis reaction. Studies were carried out to see effect of C-2 substituent of resorcinol and effect of aryl substituents, and aliphatic substituents on ring closing metathesis. This thesis describes the synthesis of bridged resorcinarenes and study of antimicrobial activity of resorcinarenes.
Thesis:
Thesis (M.S.)--University of South Florida, 2007.
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by Kirankirti Muppalla.
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Functionalization of Resorcinarenes and Study of Antimicrobial Activity by Kirankirti Muppalla A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science Department of Chemistry College of Arts and Sciences University of South Florida Major Professor: Kirpal S Bisht, Ph.D. Roman Manetsch, Ph.D. Abdul Malik, Ph.D. Date of Approval: May 21, 2007 Keywords: cavitand, ring closing metathesis crystal structure, NMR, antimicrobial activity Copyright 2007 Kirankirti Muppalla

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DEDICATION I would like to dedicate my thesis as a token of appreciation to my beloved mother Mrs. Bhanumati Muppalla who motivated me to pur sue this degree and to my father Mr. M.B.V. Subrahmanyam for his guidance. I wish to dedicate this thesis to my brother Mr. M.C. Dharmadeep for his inspiration and gui dance. I would also like to dedicate this thesis to my husband Mr. Vi nod Gudavalli for his support.

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ACKNOWLEGEMENTS I would like to sincerely acknowledge th e guidance and advice of my principal investigator Dr. Kirpal S. Bisht I woul d also like to thank my committee members Dr.Roman Manetsch, Dr. Abdul Malik fo r their valuable suggestions throughout. I would like to thank Dr. Frank Fronczek at the Louisiana State University, for his help in crystallographic analysis. I would like to thank Dr. Ted Gauthier at the University of South Florida for the mass spectra l data. I am thankful to Dr. Edwin Rivera for NMR data. I wish to thank Mr. Jason Perman for his help in crystallographic data. I wish to thank Mr. Sumedh Parulekar for working with me on this project and research work. I am thankful to my lab mates Pa sha Khan, Ruizhi Wu, Surbhi Bhatt and Meghanath Gali for their timely help and support during my research work. Last but not the least I wish to acknowle dge my husband Mr.Vinod Gudavalli for his support. Finally, I extend my thanks to Department of Ch emistry and University of South Florida for giving me an opportunity to carry out this research project succe ssfully and accomplish my goals.

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TABLE OF CONTENTS LIST OF TABLES iii LIST OF FIGURES vii LIST OF SCHEMES viii LIST OF ABBREVATIONS ix ABSTRACT x 1. CHAPTER 1. INTRODUCTION 1 1.1. Introduction to Resorcinarenes 1 CHAPTER 2. SYNTHESIS OF RESORCINARENES 6 2.1a. Synthesis of Octahydroxy Resorcinarenes with aliphatic substituents (1-4) 6 2.1b. Synthesis of Octahydroxy Resorcinarenes with Aromatic substituents (5-8) 7 2.1c. Bromination of Octahydroxy Resorcinarenes 9 2.2. Allylation of Octahydroxy Resorcinarenes 9 2.2a. Allylation of Octahydroxy Resorcinarenes (1, 2, 10, 11, 12) 9 2.2b. Allylation of Octahydroxy resorcinarenes (3, 4) 12 2.2c. Allylation of Octahydroxy compounds 5-8 13 2.3. Study of Ring closing metathesis on Resorcinarenes 15 i

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2.3a. Introduction to Ring closing metathesis 15 2.3b.Ring closing metathesis on compounds 13 and 18 16 2.3c. Ring Closing on compounds 20-23 17 2.3d Ring Closing Metathesis on Resorcinarenes 15 and 16 20 2.4. Study of Inter/Intramolecular Ring Closing 21 CHAPTER 3. LEWIS ACID CATALYZED SYNTHESIS OF RESORCINARENES FROM 2, 4-DIM ETHOXY CINNAMIC ACID AND STUDY OF RESROCINARENE'S ANTIMI CROBIAL ACTIVITY 24 3.1. Synthesis of resorcinarenes from 2, 4 dimethoxy cinnamic acid 24 3.2. Synthesis of Resorcinarenes 24 3.3. Introduction to Study of Antimicr obial activity of Resorcinarenes 27 3.4. Testing of resorcinarenes for Antimicrobial activity 28 CHAPTER 4. EXPERIMENTAL 34 4.1. General experimental procedure 34 4.2. Crystal structure data of Resorcinarenes 50 REFERENCES 52 APPENDICES 53 APPENDIX A Spectra of Compounds 54 ii

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LIST OF TABLES Table 1 Results of Ring closing metathesis 23 Table 2. Antimicrobial activity of hydroxy Resorcinarenes 32 Table 3. Antimicrobial activity of perallylated Resorcinarenes 32 Table 4. Antimicrobial activity of Me thylene bridged Resorcinarenes 33 Table 5. Antimicrobial activity of bridged Resorcinarenes 33 iii

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LIST OF FIGURES Figure 1. Structure of Resorcinarene 2 Figure 2. Conformations of Resorcinarene (Top View) 3 Figure 3. 1 H NMR Spectrum of Compound 1 8 Figure 4. 1 H NMR of compound 4 8 Figure 5. Crystal Structure of Compound 13 10 Figure 6. Crystal Structure of Compound 17 11 Figure 7. Ortep plot of compound 16 12 Figure 8. DEPT NMR of compound 21 14 Figure 9. Crystal Structure of Compound 21 15 Figure10. Grubb's generation I catalyst 16 Figure 11. DEPT 13 C-NMR of compound 29 19 Figure 12.Comparative proton NMR spectrum of compound 31 and its precursor molecule compound 16 21 Figure 13. Schematic representation fo r preparation of Petri plates 31 Figure 14. 1 H NMR of compound 1 57 Figure 15 13 C NMR of compound 1 57 Figure 16. 1 H NMR of compound 2 58 Figure 17. 13 C NMR of compound 2 58 iv

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Figure 18. 1 H NMR of compound 3 59 Figure 19. 13 C NMR of compound 3 59 Figure 20. 1 H NMR of compound 4 60 Figure 21. 13 C NMR of compound 4 60 Figure 22. 1 H NMR of compound 5 61 Figure 23 13 C NMR of compound 5 61 Figure 24. 1 H NMR of compound 6 62 Figure 25. 13 C NMR of compound 6 62 Figure 26. 1 H NMR of compound 7 63 Figure 27. 13 C NMR of compound 7 63 Figure 28. 1 H NMR of compound 8 64 Figure 29. 13 C NMR of compound 8 64 Figure 30. 1 H NMR of compound 10 65 Figure 31 13 C NMR of compound 10 65 Figure 32. 1 H NMR of compound 11 66 Figure 33. 13 C NMR of compound 11 66 Figure 34. 1 H NMR of compound 12 67 Figure 35. 13 C NMR of compound 12 67 Figure 36. 1 H NMR of compound 13 68 Figure 37. 13 C NMR of compound 13 68 Figure 38. 1 H NMR of compound 14 69 Figure 39. 13 C NMR of compound 14 69 Figure 40. 1 H NMR of compound 15 70 v

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Figure 41. 13 C NMR of compound 15 70 Figure 42. 1 H NMR of compound 16 71 Figure 43. 13 C NMR of compound 16 71 Figure 44. 1 H NMR of compound 17 72 Figure 45. 13 C NMR of compound 17 72 Figure 46. DEPT NMR of compound 18 73 Figure 47. 1 H NMR of compound 19 73 Figure 48. 13 C NMR of compound 19 74 Figure 49. 1 H NMR of compound 20 74 Figure 50. 13 C NMR of compound 20 75 Figure 51. 1 H NMR of compound 21 75 Figure 52. 13 C NMR of compound 21 76 Figure 53. 1 H NMR of compound 22 76 Figure 54. 1 H NMR of compound 23 77 Figure 55. 13 C NMR of compound 26 77 Figure 56. 1 H NMR of compound 28 78 Figure 57. 1 H NMR of compound 29 78 Figure 58. 1 H NMR of compound 30 79 Figure 59. 1 H NMR of compound 31 79 Figure 60. 13 C NMR of compound 31 80 Figure 61. 1 H NMR of compound 33 80 Figure 62. 1 H NMR of compound 34 81 Figure 63. 1 H NMR of compound 35 81 vi

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Figure 64. 1 H NMR of compound 36 82 vii

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LIST OF SCHEMES Scheme 1. Condensation reaction be tween Resorcinols and aldehydes 7 Scheme 2. Bromination of Octahydroxy Resorcinarene 9 Scheme 3. Allylation reaction of octa hydroxy resorcinarene 11 Scheme 4. Allylation reaction of octahydroxy resorcinarene 3, 4 13 Scheme 5. Allylation reaction of octahydroxy resorcinarene 5-8 14 Scheme 6. Ring Closing Metathesis of Octaallyloxy Resorcinarene 24 and 25 17 Scheme 7. Ring Closing Metathesis on Reso rcinarenes with aryl substituents 18 Scheme 8. Ring Closing Metathesis in case of met hyl C-aryl Octaallyloxy Resorcinarene 19 Scheme 9. Synthesis of Four bridged Resorcinaranes 20 Scheme 10. Study of Inter/Intr a molecular ring closing 22 Scheme 11.Esterification of Dimethoxy cinnamic acid 25 Scheme 12. Formation of C-ethyl resorcinarene 34 26 Scheme 13. Demethylat ion of compound 34 26 Scheme 14. Conversion of Ester to alcohol 27 viii

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LIST OF ABBREVIATIONS RCM Ring closing metathesis 4 BF 3 Boron trifloride 4 NBS N-Bromosuccinimide 9 NMR nuclear magnetic resonance 10 ORTEP oak ridge thermal ellipsoid plot 10 MALDI MS matrix assisted laser de sorption ionization mass spectrometry 12 APCI MS atmospheric pressure chem ical ionization mass spectrometry 13 13 C NMR carbon nuclear magnetic resonance 13 1 H NMR proton nuclear magnetic resonance 14 R f retention factor for chromatography 16 DEPT NMR distortionless enhancement by polarization transfer nuclear magnetic resonance 19 DCM dichloromethane 27 TLC thin layer chromatography 27 THF tetrahydrofuran 27 chemical shifts for nuclear magnetic resonance 34 DMSO dimethylsulfoxide 34 J coupling constant for NMR 34 ix

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m/z mass/charge for mass spectrometry 42 x

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Functionalization of Resorcinarenes a nd Study of Antimicrobial Activity KiranKirti Muppalla ABSTRACT Cavitands are very importan t class of compounds in s upramolecular chemistry. These molecules contain rigid enforced cavity,and have attracted considerable attention in supramolecular chemistry as building bloc ks for the construction of carcerands, hemicarcerands, and other host guests complexes. Nearly 40 years ago, Niederl and Vogel laid foundation for the study of such type of condensation reactions. In our laboratory we are involved in synthesis of resorcinarenes with readily available substrates such as resorcinol and aldehydes to form a cyclic tetramer. Herein, I present detailed studies about the functionalization of the synthesized tetramers and their antimicrobi al activity. Octahydroxy resorc inarenes were synthesized and perallylated which served as acyclic diene precursors for ring closing metathesis reaction. Studies were carried out to see effect of C-2 substitu ent of resorcinol and effect of aryl substituents, and aliphatic substituents on ring closing metathesis. This thesis describes the synthesis of bri dged resorcinarenes and study of antimicrobial activity of resorcinarenes. xi

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CHAPTER 1. INTRODUCTION 1.1. Introduction to Resorcinarenes Cavitands namely bridged resorcinarenes can be defined as molecules that have constrained structure large enough to host other molecules 1,2 The original term cavitand was coined by noble laureate D.J.Cram, who defined cavita nds as synthetic organic compounds with enforced cavities large enough to complex complementary organic compounds or ions 1 They have been established as fr uitful platform for the attachment of different ligating sites giving rise to ionophores fo r anions, cations, neutral molecules. 4,5,6 Resorcinarenes such as 1 ( Figure 1) are cyclic tetramers readily formed by the acid-catalyzed condensation of resorcinol with aldehydes. 1,3 Resorcinarenes have been widely exploited as a basis for making macrocyclic host molecules in a variety of supramolecular systems, These cavitands have the ability to encapsulate and stabilize guests molecules, and to catalyze chemical transformations within their microreactor" cage like structure. 7 In 1870, Adolf Von Baeyer observed a red-colored solution upon addition of concentrated sulfuric acid to an ethanolic solution of benzaldehyde and resorcinol. 8 The red-colored solution yielded, in se veral days, a crystalline compound. In 1883, Michael determined that the crystalline compound formed was from an equal number of benzaldehyde and resorcinol molecules with loss of water molecules. 9 In 1940, Vogel and Niederl 10 prepared the crystalline com pound described by Baeyer and its 1

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peracetate derivative. Molecular weight de terminations of the crystalline compound and the peracetate derivative led them to establish the ratio of the resorc inol and the aldehyde to be 4:4, i.e., each molecule of the reso rcinarene contained four molecules of the resorcinol with four molecules of the al dehyde, with loss of 4 molecules of water. 11 The crystal structure of the resorcinarene was first solved by Erdtman and coworkers in 1968. 12 HO OH HO HO R1 R1 R1 R1 OH HO OH OH R R R R R 1 = H, CH 3 OH, Br, NO 2 R = Aliphatic or Aromatic substituents Figure 1. Structure of Resorcinarene Macrocyclic ring of resorcinarenes ca n adopt five symmetrical arrangements, namely, crown, chair, boat, diamond and saddle ( Figure 2 ). 1a,b,12 However boat and chair are the two majorly preferred confor mations depending on different R and R 1 substituents on the cavitands. 13 2

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R R R R R' R' R' R' O O O O O O O O H H H H H H H H R R R' R' R' R' HO OH OH HO HO HO OH OH R R R R R' R' R' R' HO OH OH HO HO HO OH OH R R R R R' R' R' R' HO OH OH HO HO HO OH OH R R C4v: Crown C2h: Chair D 2 d: saddle C2v: boat Figure 2. Conformations of Resorcinarene (Top View) Resorcinarene cavitands are of particular inte rest due to their robus t cavity which can be modified at the upper or lower rims without compromising the structural integrity of the inner cavity. 14,1c Intramolecular cyclizations, linkage of the neighboring phenolic groups 3

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on the adjacent phenyl rings, are the method of choice which can lead to conformationally locked "bowl shaped" resorcinarene cavitands. 15 Owing to the ease of their synthesis resorcinarenes often have been used as a starting material for a wide variety of compounds. 16 Additionally, in these molecules the upper rim can be varied by different functionalities, i.e., substituents can be added between two electron releasing hydroxyl groups. Further modification have b een reported with bridging groups, e. g., methylene bridged, ethylene bridged, and propylene bridged compounds have been prepared. 17 Resorcinarenes can be prepared in high yields by condensation of resorcinol and aldehydes without using any template or high di lution techniques. In recent years, other methods of preparation of resorcinarenes have been developed. Notably, Lewis acid catalyzed tetramerization of cinnamates to a series of C-alkyl resorcinarenes has been developed by Bruno Botta et al 18 Specifically, 2, 4-dimethoxyc innamic acid was used as starting material under carefully controlled reaction conditions employing BF 3 as a lewis acid catalyst. This method allows preparat ion of the resorcinarenes with different functionalities at the lower rim, which require multi-step approach by original condensation reaction. Ring closing metathesis (RCM) is increasingly becoming an efficient approach for the synthesis of medium to large ring systems. Advancement in the design of the catalyst leading to their remarkable functi onal group tolerance, operational simplicity, high stability and commercial availability ha s greatly contributed to the popularity of the RCM reaction. In a recent report McKervey 19 and Chen 20 have reported use of RCM in bisand tetracalix[4]arenes. The bridgi ng reaction, tandem RCM ring closing, can be 4

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used to manipulate the cavity size and hence can be used to modify the properties of the cavitand. However, there has been no report in literature of RCM reaction to manipulate the cavity size in resorcinarene cavitands. In chapter 2 I will describe our effort on RCM reaction on resorcinarene and its effect on the cavity size. The ring closing metathesis reaction using Grubbs catalyst (Gen I) was investigated on perallylated resorcinarenes, where allyl groups on adjacent phenyl rings serve as acyclic diene precurs ors, led to the formation of bridged resorcinarene cavitands. The di ameter of the upper rim was thus enlarged and the cavity size can be further manipulated by functionali zation. This report disc usses in detail the effect of C-2 substituents of resorcinol along with effect of small chain aliphatic, long chain aliphatic, and aryl substituents on ring closing metathesis reaction. The pursuit of antimicrobially acti ve compounds against a variety of microorganisms is an area of intense and impor tant research. Antimicrobial activity of calixarenes was tested by Lamartine 21 et al in 2002. They conducted preliminary screening of 57 calixarenes to assay their potential as antimicrobially active compounds against Corynebacterium fusarium Of these compounds tested, calixarenes which containing sulfonate group and hydroxyl group were found to exhibit an timicrobial activity. 21 Surprisingly, there has been no report on antimicrobial activity of resorcinarenes in the literature. In the chapter 3, I report the antimicr obial activity of resorcinarenes having different side chains, substitution groups against a diverse set of bacteria and yeasts. 5

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CHAPTER 2 SYNTHESIS OF RESORCINARENES 2.1 Synthesis of Octahydroxy Resorcinarenes 2.1aSynthesis of Octahydroxy Resorcinarenes with aliphatic substituents (1-4) Resorcinarenes 1 and 2 were prepared by condensatio n of methyl resorcinol and acetaldehyde/heptaldehyde catalyzed by hydrochloric acid in ethanol ( Scheme 1) The reaction mixture was refluxed for 12hrs whic h led to precipitation of yellow-colored solids. Compounds 1 and 2 were isolated in 67% and 88% respectively. The 1 H NMR spectrum of compound 1 in DMSO d 6 recorded at 400MHz shows a single resonance for H a at 4.4 ppm (benzylic proton), H b at 8.6ppm (Hydroxy protons), H c at 1.9ppm (Ar CH 3 ), H d at 1.6ppm (CH CH 3 ) (Figure 3 ) and H a at 4.2 ppm for compound 2. The resonances match with literature reported values. 1 Resorcinarenes 3 and 4 were synthesized following a similar procedure except for the reaction temperature which was maintained at 45 o C. Products were precipitated in ice cold water as light yellow colored solids with 48% and 78% yields, respectively. The 1 H NMR spectra of compounds 3 and 4 was similar to compounds 1 and 2 except for resonance of methyl proton at 1.97 ppm. The 13 C spectrum of these compounds were interpreted and they match with literature reported values. 1 6

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2.1b Synthesis of Octahydroxy Resorcinarenes with Aromatic substituents (5-8) In a procedure similar to that described for compounds 14, resorcinarenes 5 and 6 were prepared by condensation of methyl reso rcinol and benzaldehyde/bromobenzaldehyde ( Scheme 1 ). The reaction mixture was refluxed fo r 12hrs which led to precipitation of yellow-colored solids. Resorcinarenes 5 and 6 were isolated in 88% and 90% yield, respectively. The 1 H NMR spectra of compounds 5 and 6 in DMSO-d 6 recorded at 400 MHz, showed two resonances for H a at 5.3 ppm and 6.1 ppm ( Figure 4 ) suggesting two different chemical environment around H a i.e., the compounds 5 and 6 exists in the chair conformation. Literature reports on compound 5 and 6 have confirmed their chair conformation. 1 Using a similar experimental proce dure, the condensation of resorcinol with benzaldehyde /bromobenzaldehyde gave compounds 7 and 8 in 56% and 67% yield. The structure of the compound was confirmed from their 1 H and 13 C NMR spectral data and it was found to match with the data in literature. 1 R1 OH HO HO OH HO HO R R R R R1 OH HO OH OH R1 R1 R1 R-CHO, Ethanol, HCl 1 R = CH3 R1 = CH3 2 R = C6H13 R1 = CH3 3 R = CH3 R1 = H 4 R = C6H13 R1 = H 5 R = C6H5 R1 = CH3 6 R = C6H4Br R1 = CH3 7 R = C6H5 R1 = H 8 R = C6H4Br R1= H Scheme 1 Condensation reaction between resorcinol and aldehyde 7

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The conformational analysis of the compound 1-8 revealed the existence of two distinct conformations. Compounds 1-4 with alkyl groups (from the aliphatic aldehydes) on the lower rim preferred the crown c onformation in solution, while compounds 5-8 with phenyl ring on the lower rim of the re sorcinarene were observed in the chair conformation. Figure 3 and Figure 4 shown below are the 1 H NMR spectra for compounds 1 and 6. The data is in agreement with the structures reported in literature 2 Figure 3. 1 H NMR Spectrum of Compound 1 H b H c H a H d CH3 CH3 H3C CH3 CH 3 CH3 HO OH OH HO HO HO OH OH H3C H3C Ha Hb H c Hd H a H d H c C6H4Br C6H4Br H3C CH3 CH3 CH3 HO OH OH HO HO HO OH OH BrC6H4 BrC6H4 Ha Hb H c Hd H b Figure 4. 1 H NMR Spectrum of Compound 6 8

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2.1c. Bromination of Octahydroxy Resorcinarenes Bromination of resorcinarenes 1, 2 and 9 was successfully achieved in ethyl methyl ketone (2-butanone) with NBS at room temperature ( Scheme 2). The reaction mixture was concentrated in vacuo, dissolved in methanol and was precipitated in ice cold water. HO OH HO HO R R R R H OH HO OH OH H H H HO OH HO HO R R R R Br OH HO OH OH Br Br Br NBS, 2-Butanone 1 R = CH3 10 R = CH3 2 R = C6H13 11 R = C6H13 9 R = C9H19 12 R = C9H19 Scheme 2 Bromination of Octahydroxy Resorcinarene 1 H NMR of brominated resorcinarenes 10-12 lacked the resonance for the C-2 aromatic proton at 6.3 ppm and in the 13 C NMR the C-2 (brominated carbon) was shifted upfield from 130.0 ppm to 110.0 ppm. 2.2 Allylation of Octahydroxy resorcinarenes 2.2a Allylation of Octahydroxy resorcinarenes (1, 2, 10, 11, 12) Resorcinarenes, 1, 2, 10, 11, 12 were perallylated by reaction with allyl bromide in presence of potassium carbonate in refluxing acetone ( Scheme 3). The solid residue was filtered off and the reaction mixture was concentrated in vacuo Compound 13-17 were purified by recyrstallization from 7: 3 mixture of acetone and methanol which yielded colorless crystals. Perallylation in compound 14 was confirmed from the signal's integral values in its 1 H NMR spectrum. Allylic proton (O-C H 2 ) appeared at 4.1 ppm, the 9

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vinylic proton (CH=C H 2 ) appeared at 5.0-5.2 ppm and th e non-terminal vinylic proton (C H =CH 2 ) appeared at 5.9 ppm. In the 13 C NMR spectrum, the allylic carbon appeared at 65.0 ppm, the terminal vinylic carbon a ppeared at 117.0 ppm and the non-terminal carbon appeared at 134.0 ppm. 1 H NMR of compound 13 had broad resonances, which made it difficult to assign individual resonances. Its 13 C NMR showed resonances for the allylic carbon at 74.0 ppm, the terminal vi nylic carbon appeared at 116.3 ppm and the non-terminal carbon appeared at 1 34.7 ppm. Perallylated compounds 15-17 were in accordance with compound 14. Figure 5 and 6 shows the ORTEP plot of compound 13, and 17 which confirmed the existence of molecu le in the boat conformation, with all methyl groups in axial position. The cr own conformation that existed in hydroxy resorcinarene no longer existed because of the absen ce of hydrogen bonding, a stabilizing force for the crown conformation. Figure 5. Crystal Structure of Compound 13 10

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O O O O R R R R R1 O O O O R1 R1 R1 HO OH HO HO R R R R R1 OH HO OH OH R1 R1 R1 Allyl bromide, K2CO3, Acetone Compound No R R113 14 15 16 17 CH3C6H13C6H13C9H19CH3CH3CH3Br Br Br % yield 76% 55% 68% 35% 48% Scheme 3 Allylation reaction of octahydroxy resorcinarene Figure 6: Ortep Plot Compound 17 Figure 7 shown below is the crys tal structure of compound 16, which was crystallized from mixture of acetone and methanol showing the nonyl group in axial position 11

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Figure 7: Ortep plot of compound 16 2.2b Allylation of Octahydroxy resorcinarenes (3, 4) Allylation reaction was tried on compounds 3 and 4 following the established procedure, described earlier, but the desired product yield was low. So, reaction conditions were modified and optimi zed; Allylation was performed in a pressure vessel, which allowed reaction to be performed at higher temperature and pressure ( Scheme 4 ). Reactions in pressure vessel were performed at 120 0 C, and pure products 18 and 19 were obtained upon column chromatogra phy in 78% and 22% yield, respectively. Structures of compounds 18 and 19 were analyzed by 1 H NMR and 13 C NMR. Mass spectral data (MALDI) on compound 19 [calculated m/z = 1144.77 (M + ); observed m/z =1167.985 (M+Na + )] was in agreement with the structure. 12

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O O O O R R R R R1 O O O O R1 R1 R1 HO OH HO HO R R R R R1 OH HO OH OH R1 R1 R1 Allyl bromide, K2CO3, Acetone Pressure vessel, 90-120oC 3 R = CH3 R1 = H 4 R = C6H13 R1 = H 18 R = CH3 R1 = H 19 R = C6H13 R1 = H Scheme 4 Allylation reaction of octahydroxy resorcinarene 3, 4 2.2c Allylation of Octahydroxy compounds 5-8 Resorcinarenes 5-8 were perallylated using acetone as a solvent and potassium carbonate as a base in 46-68% yield ( Scheme 5). It is important to point out that we also investigated a number of bases (NaH, KO t Bu, etc.) in DMF but a complex mixture of products with low yield became a problem. Als o, the removal of DMF by distillation was tedious and might have attributed to the decomposition or side reactions. Compounds 2023 were analyzed by 1 Hand 13 C NMR and APCI MS data. 1 H NMR spectrum clearly showed the changes occurred between 4.0 and 6.0 ppm after perallylation reaction. Allylic proton (O-C H 2 ) appeared between 4.0-4.4 ppm, the vinylic proton (CH=C H 2 ) appeared between 5.0-5.4 ppm and the non-terminal vinylic proton (C H =CH 2 ) appeared between 5.8-6.0 ppm ( Figure 8 ). In the 13 C NMR spectrum, the allylic carbon appeared between 65.0-75.0 ppm, the terminal vinylic carbon appeared between 115.0-120.0 ppm and the non-terminal carbon peak ap peared between 125.0-130.0 ppm. 13

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O O O O R R R R R1 O O O O R1 R1 R1 HO OH HO HO R R R R R1 OH HO OH OH R1 R1 R1 Allyl bromide, K2CO3, Acetone 5 R = C6H5 R1 = CH3 6 R = C6H4Br R1 = CH3 7 R = C6H5 R1 = H 8 R = C6H4Br R1 = H 20 R = C6H5 R1 = CH3 21 R = C6H4Br R1 = CH3 22 R = C6H5 R1 = H 23 R = C6H4Br R1= H Compound No DMF/KOtBuAcetone/K2CO320 21 22 23 48% 68% 46% 65% 54% 68% 57% 70% Scheme 5 Allylation reaction of octahydroxy resorcinarene 5-8 Figure 8: 1 H NMR spectrum of compound 21 H b H c H a H c H d C6H4Br C6H4Br H3C CH3 CH3 CH3 O O O O O O O O BrC6H4 BrC6H4 Ha Hb Hc Hd Hd He 14

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Compound 21 was recyrstallized as light yellow colored crystals from acetone and methanol solvent (7:3) system. The ORTEP plot of compound 21 ( Figure 9) shows the resorcinarene ring in the preferred chair conformation with the allyloxy groups on upper rim and the two phenyl rings in axial positi on and other two in equatorial position Figure 9. Crystal Structure of Compound 21 2.3. Study of Ring closing metathesis on Resorcinarenes 2.3a Introduction to Ring closing metathesis Intramolecular cyclizations leading to a bridge d structure have been a very important to the synthesis of many cavitands. Ring-closing metathesis (RCM) is becoming a preferred approach to synthesis of medium and large si zed macrocyclic molecules. Resorcinarenes have two well-defined rims; a lower rim de fined by alkyl or phenyl substituents from corresponding aldehyde and an upper rim defined by hydroxyl groups of resorcinol. The RCM reaction on perallylated resorcinarenes can be utilized to manipulate the cavity size. 15

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In this chapter, I report the RCM reaction on resorcinarenes with small aliphatic chain, longer aliphatic chain, and aroma tic rings. Also effect of the resorcinol's C-2 substituent on RCM was investigated. Grubbs generation I catalyst, which has been widely used for ring closing metathesis due to its remarkab le functional group tolerance, operational simplicity, high stability and commercial availa bility was utilized in this investigation. Interesting conformational dynamics in the octaallyloxy resorcin arene, due to its flexibility, ( Figure 10 ) resulted in interesting observations summarized in the following sections. Figure 10. Grubb's generation I catalyst. 2.3b Ring closing metathesis on compounds 13 and 18 Resorcinarenes 13 and 18 were subjected to RCM to obtain compounds 24 and 25, respectively ( Scheme 6 ). The reactions were carried ou t under nitrogen atmosphere in dry dichloromethane using 8 mol % of Grub bs catalyst (Gen I). The reaction was monitored for 4 days. The desired product was separated by column chromatography in 13-16% yield. Starting mate rial was recovered by colu mn chromatography and was reused in subsequent reaction. The charac terization was done by mass spectral data and 13 C data. In the 13 C NMR spectrum of compound 24 [APCI MS m/z =893.5 (M+H + )], the terminal allylic carbon (C= C H 2 ) resulted in two resona nces at 117.0, 117.8 ppm; the OC H 2 carbon region had three peaks at 70.0, 73.0 74.0, ppm; the non terminal vinylic carbon was observed as three different resonances at 133.0, 133.7, 134.2 ppm. A careful 16

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analysis of the NMR data and its molecula r weight suggested formation of the one bridged cavitand. The multiplicities in the 13 C NMR spectrum can be explained considering that the structure 24 has a plane of symmetry. Ma ss spectral data (APCI MS) on compound 24 [calculated m/z = 892.49 (M + ); observed m/z =893.5 (M+H + )] 25 [calculated m/z = 836.43 (M + ); observed m/z =837.4 (M+H + )] was in agreement with the structure. O O O O R R R R R1 O O O O R1 R1 R1 Grubb's catalyst, Dry DCM R.T., 4 days24 R1 = CH3 25 R1 = H 13 R1 = CH3 18 R1 = H O O O O R R R R R1 O O O O R1 R1 R1 Scheme 6. Ring Closing Metathesis of Octaallyloxy Resorcinarene 24 and 25. 2.3c. Ring Closing on compounds 20-23 Compounds 20-23 were treated with Grubbs catalyst (Gen I) under conditions described earlier, leading to formation resorcinarene 26-29 in 17-22% yield. Several reactions were performed with increasing concentration of Grubbs catalyst (5-10 mole %), but without increased product yields. Products were isolated by column chromatography using 6% ethyl acetate and hexane mi xture as an eluent. Scheme 7 shown below is the top view representation of the synthetic scheme. 17

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R R R1 R1 R1 R1 O O O O O O O O R R Grubb's catalyst I 5-8mol% DCM R R R1 R1 R1 R1 O O O O O O O O R R 26 R = Ph R' = H 27 R=PhB r R' = H Scheme 7. Ring Closing Metathesis on Resorc inarenes with aryl substituents 1 H NMR data had overlapping, broad resonances and could not be used for confirmation of the structure. Therefore, 13 C NMR data was used because of its wider (0-200 ppm) and sharp carbon resonances. Careful analys is of the products suggested a two bridged cavitand. The two fold symmetry, indicate d by the doubling of the carbon resonances upon bridge formation, suggested the two bridge s were formed across form each other. MALDI Mass spectral measurements confirmed the structure as a two bridged structure; 26 Mass spectral data (APCI MS ) on compound 26 [calculated m/z = 1056.00 (M + ); observed m/z =1056.46 (M + )], 27, [calculated m/z = 1368.10 (M + ); observed m/z =1385.00 (M + + H 2 O )] were in agreement with the st ructure of the respective compounds Unfortunately, the compound could not be cr ystallized for x-ray diffraction data collection. Following a similar reaction procedure, compound 28 and 29 were synthesized via ring closing metathesis of th eir respective allyloxy precursors 11 and 12 ( Scheme 8). A detail structural analysis of the products was undertaken. The 1 H and 13 C NMR data suggested formation of a single bridged compound. 18

PAGE 33

R R R1 R1 R1 R1 O O O O O O O O R R Grubb's catalyst I 5-8mol% DCM R R R1 R1 R1 R1 O O O O O O O O R R 28 R = Ph R' = CH3 29 R = PhB r R' = C H 3 Scheme 8 Ring Closing Metathesis in case of methyl C-aryl Octaallyloxy Resorcinarene MALDI Mass spectral data on compound 28 [calculated m/z = 1140.55 (M + ); observed m/z =1163.48 (M+Na + )], 29 [calculated m/z = 1456.20 (M + ); observed m/z =1479.54 (M+Na + )] was in agreement with the structure. Yields in both cases were around 10%. R R H3C CH3 CH3 CH3 O O O O O O O O R R a b c d e e a b d c,c Figure 11. DEPT 13 C-NMR of compound 29 19

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2.3d Ring Closing Metathesis on Resorcinarenes 15 and 16 The perallylated resorcinarenes 15 and 16 served as acyclic diene precursors for ring closing metathesis reaction. Compounds 15, 16 were treated with Grubbs catalyst (Generation I) in dichloromethane ( Scheme 9 ). Reaction was carried out at room temperature for 96 hrs which led to the obser vation of two spots having lower Rf value than starting substrate on thin layer chromatography. The reaction mixture was subjected to column chromatography in 6% ethyl acetate and hexane. The compound 30 and 31 were isolated in 23% and 32%, respectively. The absence of the terminal vinylic proton (-C=CH 2 ) peak at 4.5 ppm in 1 H NMR and at 117.0 ppm in 13 C NMR spectra suggested formation of a bridged cavitands. Figure 12 shown below is the comparative proton spectrum of compound 31 with its precursor molecule compound 16. O O O O R R R R Br O O O O Br Br Br O O O O R R R R Br O O O O Br Br Br Grubb's Catlyst-I Dichloromethane, RT 5-8 mol% 15 R= C6H13 30 R= C6H13 16 R= C 9 H1 9 31 R= C 9 H1 9 Scheme 9. Synthesis of Four bridged Resorcinaranes 20

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c B A C A B Vinylic proton disappears 1 H NMR(250MHz) e b C O O O O O O O O C6H13C6H13C6H13 Br Br Br Br g h m n o b c f e if g -n o Figure 12. Comparative proton NMR spectrum of compound 31 and its precursor molecule compound 16 2.4. Study of Inter/Intramolecular Ring Closing To understand ring closing metathesis and inve stigate the intraor intermolecular ring formation we subjected perall ylated resorcinol to RCM reaction using Grubbs catalyst. Reactions were tried with varying reaction concentration and mol % of catalyst. The intra-molecular ring closing was never observed. 21

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OH HO R K2CO3,Acetone Allyl bromide R O O R = CH3R = H Grubb's catalyst-I DCM R O O Scheme 10. Study of Inter/Intra molecular ring closing Energy minimization calculation using MM2 MODEL on the resorcinarene 13, indicated that the intermolecular ring clos ed structure was about 6 Kcal less that the intermolecular ring closed structure. 22

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Summary Below given is the table wh ich summarizes the data.( Table 1 ) Compound No: R R 1 Bridges formed 24 CH 3 CH 3 one 25 CH 3 H one 30 C 6 H 13 Br four 31 C 9 H 19 Br four 28 C 6 H 5 CH 3 one 29 C 6 H 4 Br CH 3 one 26 C 6 H 5 H two 27 C 6 H 4 Br H two Table 1 : Results of Ring closing metathesis Conclusion In conclusion to this study, I have investigated the effect of alkyl and aryl substituent on ring closing metathesis. It was observed th at longer hydrophobic aliphatic chains favor ring closing metathesis. It was also observe d formation of four bridged compound is more favored in compounds with crown c onformation over chair conformation. From the studies described in this chapter bulky groups at C-2 position of resorcinol favor ring formation. When smaller group such as hydrogen is present it does not favor ring formation due to steric effects. 23

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CHAPTER 3 LEWIS ACID CATALYZED SYNTHESIS OF RESORCINARENES FROM 2, 4DIMETHOXY CINNAMIC ACID AND STUDY OF RESROCINARENE'S ANTIMICROBIAL ACTIVITY 3.1 Synthesis of resorcinarenes from 2, 4 dimethoxy cinnamic acid Bruno 20 et al first described the Lewis acid catalyzed synthesis of resorcinarene starting form 2,4dimethoxycinnamic acid. It involve d esterification of 2, 4-dimethoxy cinnamic acid followed by treatment with BF 3 etherate under carefully controlled conditions leading to the formation of tetramerized resorcinarenes. Influence of Lewis acid, temperature, and reaction time and their e ffects on the resorcinar ene conformation had also been described. Interestingly, it was noted that longer reaction times always led to chair conformation. Using the procedur e described by Bruno et al., compound 33 was isolated after a reaction time of 10hrs. This chapter discusses in detail the strategy I employed in preparation of resorcin arenes and their functionalization. 3.2 Synthesis of resorcinarenes Another high yielding synthesis of resorcin arenes involves the lewis acid catalyzed tetramerization of 2, 4-dimethoxy cinnamate s. The synthesis began with the base catalyzed esterification of our starting mate rial 2, 4-dimethoxy cinnamic acid in acetone 24

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with potassium carbonate and ethyl iodide The reaction was refluxed for 12hrs and filtration of the solid provide d us with quantitative yield of ethyl ester of dimethoxy cinnamic acid. Scheme 12 shown below is the esterifi cation reaction. The compound was characterized by 1 H NMR; the ethyl ester resonanc es were observed at 1.34 ppm (t, J=7.25) for (CH 2 CH 3 ), 4.24 ppm (q, J= 7.25) for ( CH 2 CH 3 ). OMe MeO O OH OMe MeO O O EtI, Acetone, K2CO3 Reflux 12 hrs33 Scheme 11: Esterification of Di methoxy cinnamic acid The ester 33 was treated with BF 3 etherate in chloroform at room temperature for 10 hrs, after which the reaction was quenched with methanol and concentrated in vacuo The product 34 was isolated by column chromatogra phy in 6% methanol/dichloromethane mixture in 67% yield. The co mpound was analyzed by NMR. 1 H NMR1.03 ( d, J= 9Hz ) for methyl protons, 2.87 (d, J= 7.75Hz) for ArCH CH 2 3.5ppm (s) for OCH 3 protons, 3.72 ( q, J=4.75Hz) for CH 2 CH 3 4.86 (s) for benzylic proton, 6.19 ( d, J= 9.75hz), 6.54 (s ) for aromatic protons co nfirmed that compound exist in crown conformation with the ethyl groups all pointi ng in axial position. The NMR data was in agreement with the data reported in the literature. 20 25

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OMe MeO O O CH2COOEt EtOOCH2C EtOOCH2C CH2COOE t OMe OMe OMe MeO MeO MeO MeO OMe BF3Et2O, CHCl3RT, 10 hrs34 33 Scheme 12: Formation of C-ethyl resorcinarene 34 The compound 34 was subjected to demethylation using aluminum trichloride in dichloromethane ( Scheme 14). The reaction was performed at room temperature for 12 hrs, diluted with dichloromethane and washed with 100ml of water, brine and was separated on a column with 44% yield. The compound was analyzed by NMR which showed resonance for methoxy as well as hyd roxyl protons indicati ng that the compound was partially demethylated to compound 35. CH2COOEt EtOOCH2C EtOOCH2C CH2COOEt OMe OMe OMe MeO MeO MeO MeO OMe 33 AlCl3, DCM, RT CH2COOEt EtOOCH2C EtOOCH2C CH2COOEt OH OMe OH HO MeO MeO MeO OMe 35 Scheme 13: Demethylation of compound 35 Compound 34 was subjected to reduction using lithium aluminium hydride in THF. The reaction was monitored by TLC. LAH wa s added to reaction mixture at 0 0 c and reaction 26

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mixture was allowed to warm up to room te mperature. Reaction wa s carried out for 10 hrs after which it was quenched by 0.5ml of water, 0.5ml of saturated sodium chloride solution and extracted into DCM in a seperatory funnel. It was concentrated in vacuum, dried and NMR of the product was taken, wh ich indicated the conve rsion of ester to primary alcohol in 56% yield. New res onance was found for hydroxyl groups at 2.0 ppm with absence of resonances for ethyl peaks. Scheme 15 shown is the reduction reaction of ester to alcohol. CH2COOEt EtOOCH2C EtOOCH2C CH2COOEt OMe OMe OMe MeO MeO MeO MeO OMe 34 LAH, THF, RT CH2CH2OH HOH2CH2C HOH2CH2C CH2CH2OH OMe OMe OMe MeO MeO MeO MeO OMe 36 Scheme 15: Conversion of Ester to alcohol To the conclusion of this chap ter, I have employed the easie r route in the synthesis of resorcinarenes that cannot be synthesized by normal condensation method. 3.3 Introduction to Study of Antimicrobial activity of Resorcinarenes The pursuit of antimicrobially active compounds against a wide variety of microorganisms is an area of intense and im portant research. Antimicrobial activity of calixarenes was tested by Lamartine 21 et al in 2002. In the present study, we examined the relative antimicrobial activity of reso rcinarenes having different side chains, substitution groups against bacteria and yeasts Antimicrobial activity against the various 27

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species was evaluated by zone of inhibition to distinguish between the compounds for this desired property. 21 Calixarenes can be modified fo r host molecules with defined structure and function. I have tested resorcinarenes agains t wide variety of bacteria includes ( P. aeruginosa S. aureus M.luteus E. coli B. subtilis ) and yeasts( C. albicans ). Not much research was carried ou t in this field, so we have choosen this area of interest to test the compounds for desired property. 3.4. Testing of resorcinarenes for Antimicrobial activity I employed Kirby Bauers di sk diffusion method which a standard method that has been used for years to test the compounds for antimic robial activity and is initial stage to test the activity of compounds. The disk-diffusion method (Kirby-B auer) is more suitable for routine testing in a clinical laboratory wher e a large number of isolates are tested for susceptibility to numerous antibiotics. An agar plate is uniformly inoculated with the test organism and a paper disk impregnated with a fixed concentration of an antibiotic is placed on the agar surface. Growth of the organism and diffusion of the antibiotic commence simultaneously resulting in a circular zone of inhibition in which the amount of antibiotic exceeds inhibitory concentrations The diameter of the inhibition zone is a function of the amount of drug in the disk and susceptibility of the microorganism. 28

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3.4a Preparation of Agar plates Below shown are the organisms that are empl oyed for testing and nutrient media used for their growth. a) Bacillus subtilis b) Micrococcus luteus Nutrient medium c) Pseudomonas aeruginosa d) Candida albicans Saboraud Medium e) Escherichia coli Liquid broth f) Staphylococcus aureus Preparation of Nutrient /Liquid /Saboraud medium 11.5 g of nutrient agar/20gof LB / 32.5g of Saboraud media that is available commercially were taken into clean 500mL deionized water, heated till the mixture was homogenous. It was autoclaved for 17 min at temperature of 121 0 C to sterilize the media .It was carefully removed from autoclave and cooled down to 50 0 C and 20ml of this media was poured into Petri plates under aseptic conditions. The Pe tri plates were allowe d to cool to room temperature and can be used as and when needed. Preparation of Broth for growth of Organisms The broth was prepared similarly to the above described procedure, broth media was used instead. 20ml aliquot of this solution was ta ken into test tubes and used when needed 29

PAGE 44

Preparation of Single colony of organism In order to test the activity of compound it was always advisa ble that single colony of the organism to be tested. The single colony of the organism was prepared by taking the organism culture and streaking the organism onto Petri plate cont aining the appropriate medium for growth. It was incubated for 2 days at 37 0 C in incubator, when the growth was seen, a single colony from this Petri pl ate was transferred into broth medium under aseptic conditions and allowed to incubate for 2 days on a rotary shak er. This culture is good for 2 weeks if stored in the refrigerator. Below shown ( Figure 13 ) is the schematic representation of above described procedure. Preparation of Discs Paper discs are available commercially. The co mpound to be tested (2 5mg) is taken into clean vial and diluted with miscible solvent to 1ml. 40L of this solution contains 1mg of compound 4ul contains 0.1mg and 0.4ul contai ns 0.01mg. The appropriate solution of this was transferred onto paper discs using microlitre pipettes and was dried carefully. Transfer of Discs on to Agar media The agar filled plates are warmed to 37 0 C in incubator for 2 hrs before the transfer of discs. The organism was streaked onto agar plates and compound filled disc was carefully transferred onto Petri plate under aseptic conditions. It was incubated at ambient temperature for 1 day and zone of inhibition if seen was noted. 30

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Nutrient medium Incubate for 1-2 days Autoclaving Preparation of Petri plates Streaking Transfer of single colo ny into nutrient medium Shake it for one day till you see turbidity Spread small amount of above solution ont o fresh Petri plate and place the compou nd filled d i s c and incubate for nearl y one da y Schematic represen tation Figure 13 : Schematic representation for preparation of Petri plates Results and Discussion I have te ste d 30 r e sorc inarenes f o r antim icrobia l ac tiv ity. The resu lts a r e summ arized in following tables. It was observed that(1) reso rcinarenes prepared from resorcino l had higher activ ity than tho s e f r om m e thyl reso r c inol, (2 ) th e ally la tion of the phen o lic hydroxyl resulted in decreased potency, (3) Pr esence of polar groups on the upper rim led to higher potency. 31

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Structure of compound R R 1 Zone of Inhibition Organism CH 3 C 6 H 13 CH 3 CH(CH 2 CH 3 ) 2 CH 3 CH 3 H CH 3 H C 6 H 13 H C 9 H 19 H CH(CH 2 CH 3 ) 2 12mm M .luteus H C 6 H 5 H C 6 H 4 Br 9mm M .luteus OH OH HO OH OH HO HO HO R R R R1 R R1 R1 R1 H C 6 H 4 Cl Table 2 : Antimicrobial activity of Hydroxy Resorcinarenes Structure of compound R R 1 Zone of Inhibition Organism CH 3 C 9 H 19 CH 3 CH(CH 2 CH 3 ) 2 CH 3 CH 3 H C 6 H 13 8mm P. aeruginosa M. luteus H C 9 H 19 H CH(CH 2 CH 3 ) 2 H C 6 H 5 8mm S. aureus H C 6 H 4 Br O O O O O O O O R1 R1 R1 R1 R R R R H C 6 H 4 Cl 8mm P aeruginosa M luteus E .coli S .aureus Table 3 : Antimicrobial activity of Perallylated Resorcinarenes 32

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Structure of compound R R 1 Zone of Inhibition Organism CH 2 Br C 6 H 13 CH 2 CH 2 COOH C 6 H 13 12mm 10mm 8mm M .luteus S. aureus E .coli CH 2 (CHCOOEt) 2 C 6 H 13 CHCH 2 COOCH 3 C 6 H 13 CH 2 (CHCH 2OGlu) 2 C 6 H 13 CH 2 (CHCH 2 OH) 2 C 6 H 13 CH 3 C 6 H 5 O O O O O O O O R1R1R1R1 R R1 R1 R1 CH 3 C 6 H 4 Br Table 4: Antimicrobial activity of Meth ylene Bridged Resorcinarenes Structure of compound R R 1 Zone of Inhibition Organism CH 3 C 6 H 13 O O O O O O O O R1R1R1R1 R R R R CH 3 CH(CH 2 CH 3 ) 2 Table 5 : Antimicrobial activity of bridged Resorcinarenes In conclusion to this study, we have obs erved antimicrobial activity on certain resorcinarenes which had hydrogen in C-2 position of resorcinol. Further extensive studies have to be carried out to figure the antimicrobial activity of resorcinarenes on wide variety of b acteria and fungi. 33

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CHAPTER 4 EXPERIMENTAL SECTION 4.1 General experimental procedure All solvents and reagents were commercially available. Heptanal was purified by distillation. NMR spectra were recorded on 250 MHz, 400 MHz and 500 MHz spectrometers. Mass spectra were record ed in APCI mode and using MALDI. Synthesis of octahydroxy resorcinarene (1): Methyl resorcinol (10g, 0.081mol) was dissolved in (62.7mL, 775mL/mol) ethanol and (14.9mL, 185mL/mol) 37% aqueous HCl. The solution was cooled in ice bath a nd (3.56mL, 0.081mol) acetaldehyde (which was maintained at 0 0 C) was added to above solution slowly over a period of 30 min. Then the mixture was allo wed to warm to room temperature. The reaction was refluxed for nearly 12 hrs. Then the reaction mi xture was poured onto 500mL of ice cold water. So obtained ye llow colored precipitate was filtered through buchner funnel and the precipitate is washed several times until it turns neutral to pH paper. It is dried and NMR was taken in DMSO d 6 It was synthesized in 67% yield (8.4g). 1 H NMR (DMSO) 1.75(d, 12H J= 7.5Hz ), 1.93(s, 12H), 4.4 (q, 4H J= 7.5Hz ), 7.4 (s, 4H,), 8.7(s, 8H). Synthesis of octahydroxy resorcinarene (2): Methyl resorcinol (10g, 0.081mol) was dissolved in (62.7mL, 775mL/mol) ethano l and (15.1mL, 185mL/mol) 37% aqueous HCl. The solution was cooled in ice bath and (11.3mL, 0.081mo l) heptaldehyde was 34

PAGE 49

added to above solution slowly over a period of 30 min. Then the mixture was allowed to warm to room temperature. The reaction refl uxed for nearly 12 hrs after which I observed yellow colored precipitate. So obtained prec ipitate was filtered through buchner funnel and the precipitate is washed several times unt il it turns neutral to pH paper. It is dried and NMR was taken in DMSO d 6 (250MHz). It was synthesized in 88 % (10.7g) yield. 1 H NMR (DMSO) 0.84 (t, 12H, J = 6.25Hz )), 1.23(m, 32H), 1.93(s, 12H), 2.21(s, 8H), 4.18 (t, 4H J = 7.75Hz )), 7.21 (s, 4H), 8.69(bs, 8H). Synthesis of octahydroxy resorcinarene (3): Resorcinol (10g, 0.091mol) was dissolved in mixture of 35mL ethanol, 35mL of wa ter and (16.8mL, 775mL/mol) 37% aqueous HCl. The solution was cooled in ice bath and acetaldehyde (4 mL, 0.091mol) was added to above solution slowly over a period of 30 min. Then the mixture was allowed to warm to room temperature and allowed to stir at room temperature for nearly one day. Then the reaction mixture was poured into 500mL of i ce cold water .So obtained light yellowed colored precipitate was filtered through buchne r funnel and the precipitate is washed several times until it turns neutral to pH pa per. It is dried and NMR was taken in DMSO d 6 It was synthesized in 48% (4.23g) yield. 1 H NMR (DMSO) 1.29 (d, 12H, J = 7.0Hz)), 1.93(s, 3H ), 4.4(q, 4H, J= 7.5Hz)), 7.4(s, 4H), 8.7(s, 8H). Synthesis of octahydroxy resorcinarene (4): -Resorcinol (10g, 0.091mol) was dissolved in (71mL, 775mL/mol) ethanol and (16.8m L, 185mL/mol) 37% aqueous HCl. The solution was cooled in ice bath and (12.7m L, 0.091mol) heptaldehyde was added to above solution slowly over a period of 30 min. Then the mixture was allowed to warm to room temperature. The reaction was th en maintained at temperature of 60 0 C for nearly 36 35

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hrs. Then the reaction mixture was poured onto 500mL of ice cold water .So obtained precipitate was filtered through buchner funne l and the precipitate is washed several times until it turns neutral to pH paper. It is dried and NMR was taken in DMSO d 6 It was synthesized in 78% (8.4g) yield. 1 H NMR (DMSO) 0.82 (t, 12H), 1.21 (m, 32H) 2.07 (m, 8H), 4.23 (t, 4H), 6.13 (s, 4H), 7.12 (s, 4H), 8.55 (s, 8H). Synthesis of octahydroxy resorcinarene (5): Methyl resorcinol (10g, 0.081mol) was dissolved in (62.7ml, 775mL/mol) anhydrous ethanol and (15.1mL, 185mL/mol) 37% aqueous HCl.The solution was cooled in i ce bath and (7.6mL, 0.081mol) benzaldehyde was added to above solution slowly over a period of 30 min. Then the mixture was allowed to warm to room temperature. The reaction was then maintained at temperature of 80 0 C for nearly 12 hrs, forms yellow colored precipitate .So obtai ned precipitate was filtered through buchner funnel and the precipitat e is washed several times until it turns neutral to pH paper. It is dried and NMR was taken in DMSO d 6 (250Hz). It was obtained in 88% (8.4g) yield. 1 H NMR (DMSO) 1.9 (d, 12H), 5.25 (s, 2H), 5.6(s, 4H), 6.1 (s, 2H), 6.6 (d, 8H), 7.1 (d, 12H), 7.6 (d, 8H). Synthesis of octahydroxy resorcinarene (6): Methyl resorcinol (10g, 0.081mol) was dissolved in (62.7mL, 775mL/mol) ethano l and (15.1mL, 185mL/mol) 37% aqueous HCl.The solution was cooled in ice bath and (14.4g, 0.081mol) bromobenzaldehyde was added to above solution slowly over a period of 30 min. Then the mixture was allowed to warm to room temperature. The reaction wa s then maintained at temperature of 80 0 C for nearly 12 hrs after which I observe formati on of yellow colored precipitate .So obtained 36

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precipitate was filtered through buchner funne l and the precipitate is washed several times until it turns neutral to pH paper. It is dried and NMR was taken in DMSO d 6 (250Hz).Compound 6 was synthesized in 90 % ( 8.8g) yield. 1 H NMR (DMSO) 1.9 (d, 12H), 5.25 (s, 2H), 5.6 (s, 4H), 6.1 (s, 2H,), 6.6 (d, 8H), 7.1 (d, 8H), 7.6 (d, 8H). Synthesis of octahydroxy resorcinarene (7): Resorcinol (10g, 0.091mol) was dissolved in (71mL, 775mL/mol) ethanol and (16.8m L, 185ml/mol) 37% aqueous HCl. The solution was cooled in ice bath and (8.8mL, 0.091mL/mol) benzaldehyde was added to above solution slowly over a period of 30 min using syringe. Then the mixture was allowed to warm to room temperature. The reaction was then maintained at temperature of 80 0 C for nearly 12 hrs after which we can see yellow colored precipitate. So obtained precipitate was filtered through Buchner funne l and the precipitate is washed several times until it turns neutral to pH paper. It was synthesized in 56% (5.34g) yield. NMR was taken in DMSO 1 H NMR (DMSO) 5.65 (s, 4H), 6.17 (s, 4H), 6.32 (b s, 4H), 6.72-6.8 (m, 8H), 6.927.02 (m, 12H), 8.88 (d, 8H). Synthesis of octahydroxy resorcinarene (8): Resorcinol (10g, 0.091mol) was dissolved in (71mL, 775mL/mol) ethanol and (16.8m L, 185mL/mol) 37% aqueous HCl. The solution was cooled in ice bath and ( 16g, 0.091mol) bromobenzaldehyde was added to above solution slowly over a period of 30 min using syringe. Then the mixture was allowed to warm to room temperature. The reaction was then maintained at temperature of 80 0 C for nearly 12 hrs after which we can see yellow colored precipitate. So obtained precipitate was filtered through buchner funne l and the precipitate is washed several 37

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times until it turns neutral to pH paper. It is dried and NMR was taken in DMSO It was synthesized in 67% (6.3g) yield. 1 H NMR (DMSO) 5.32 (s, 2H), 5.48 (d, 2H), 6.14 (s, 2H), 6.2 (d, 2H), 6.58 (d, 8H), 6.62 (d, 0.5H), 6.94 (d, 8H), 7.02 (d, 2H), 8.7 (d, 8H). Synthesis of Octahydroxy Resorcinarene (10) :1g of Octahydroxy resorcinarene 1 was taken in 2butanone (10mL/mmol) into round bottomed flask, stirred for 10 min. 6 eq of N-bromo succinimide was adde d to the above stirred so lution in small amounts and reaction was stirred at room temperature for 12 hours. Re action was monitored by thin layer chromatography. 2Butanone was evap orated on Rota vapor which resulted in yellow color precipitate which was filtered and washed with cold 2butanone. NMR was taken in DMSO. 1.42 (d,12H), 4.62 (d,4H), 6.82 (s,4H), 8.38 (s,8H). Synthesis of Octahydroxy Resorcinarene (11) :1g of Octahydroxy resorcinarene 2 was taken in 2butanone (10mL/mmol) into round bottomed flask, stirred for 10 min. 6 eq of N-bromo succinimide was adde d to the above stirred so lution in small amounts and reaction was stirred at room temperature for 12 hours. Re action was monitored by thin layer chromatography. 2Butanone was evap orated on Rota vapor which resulted in yellow color precipitate which was filtered and washed with cold 2butanone. NMR was taken in DMSO. 0.84 (s, 12H), 1.24 (s 32H) 2.2 (s,8H), 4.35 (t,4H), 7.35 (s,4H), 9.1 (s,8H). Synthesis of Octahydroxy Resorcinarene (12) :1g of Octahydroxy resorcinarene in 2butanone (10mL/mmol) was taken into round bottomed flask, stirred for 10 min. 6 eq of N-bromo succinimide was adde d to the above stirred so lution in small amounts and reaction was stirred at room temperature for 12 hours. Re action was monitored by thin 38

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layer chromatography. 2Butanone was evap orated on Rota vapor which resulted in yellow color precipitate which was filtered and washed with cold 2butanone. NMR was taken in DMSO. 0.84 (s, 12H), 1.24 (s, 54H), 2.2 (s,8H), 4.35 (t,4H), 7.35 (s,4H), 9.1 (s,8H). Synthesis of octaallyloxy resorcinarene (13): 1g of Octahydroxy compound 1 was taken into round-bottomed flask and (20mL/mol) acetone was added to RBF. The reaction mixture was stirred till homogenous mixt ure was formed. Then (30eq) potassium carbonate was slowly added over a period of ha lf an hour where the reaction mixture is ice cooled. Here we observe the change in co lor from brown to purple. Then the reaction mixture was brought to room temperature and (30eq) allyl bromide was added. The reaction mixture was heated to temperature of 60 0 C for nearly 24-48 hrs. The reaction mixture was filtered and then concentrated and was recrystallized using 70% acetone methanol mixture. It was synthesized in 76% (1.2g) yield. Dept 135 was taken on this compound since the proton NMR of this compou nd gave broad peaks. Peaks at following ppm values were observed. (in ppm ) 10.54, 20.96, 32.79, 73.25, 116.12, 123.67, 134.49. Synthesis of octaallyloxy resorcinarene (14): 1g of Octahydroxy compound 2 was taken into round-bottomed flask and (20mL/mol) acetone was added to RBF. The reaction mixture was stirred till homogenous mixt ure was formed. Then (30eq) potassium carbonate was slowly added over a period of ha lf an hour where the reaction mixture is ice cooled. Here we observe the change in co lor from brown to purple. Then the reaction mixture was brought to room temperature and (30eq) allyl bromide was added. The 39

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reaction mixture was heated to temperature of 60 0 C for nearly 24-48 hrs. It was synthesized in 55% yield (0.7g). 1 H NMR (CDCl 3 ) 0.8 (t, 12H), 1.2 (m, 56H) 1.85 (m, 8H), 2.15 (s, 12H), 4.25 (dd, 16H), 4.55 (t, 4H), 5.2 (dd, 16H) 6.1 (m, 8H), 6.55 (s, 4H); 13 C NMR 10.6, 14.2, 22.8, 28.6, 29.5, 30.2, 32.1, 34.1, 35.4, 36.5, 40.0, 73.3, 116.2, 124.0, 133.9, 153.6. Synthesis of octaallyloxy resorcinarene (15): 1g of Octahydroxy bromo compound 11 was taken into round-bottomed flask and (20mL/mol) acetone was added to RBF. The reaction mixture was stirred till homogenous mi xture was formed. Then (30eq) potassium carbonate was slowly added over a period of ha lf an hour where the reaction mixture is ice cooled. Here we observe the change in co lor from brown to purple. Then the reaction mixture was brought to room temperature and (30eq) allyl bromide was added. The reaction mixture was heated to temperature of 60 0 C for nearly 24-48 hrs. The reaction mixture was filtered and then concentrated and was recyrstallized using 70% acetone methanol mixture. NMR was taken in CDCl 3 0.77 (t, 12H), 1.16 (d, 32H), 1.48 (t,8H), 1.82 (s,4H), 4.36 (t,16H), 5.14 (d,16H), 5.92 (s,8H). 13 C : 14.3, 22.8, 22.9, 28.8, 29.8, 32, 32.1, 35.0, 39.4, 74.1, 110.0, 117.4, 126, 133.9, 154. Synthesis of octaallyloxy resorcinarene (16): 1g of Octahydroxy bromo compound 12 was taken into round-bottomed flask and (20mL/mol) acetone was added to RBF. The reaction mixture was stirred till homogenous mi xture was formed. Then (30eq) potassium carbonate was slowly added over a period of ha lf an hour where the reaction mixture is ice cooled. Here we observe the change in co lor from brown to purple. Then the reaction mixture was brought to room temperature and (30eq) allyl bromide was added. The 40

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reaction mixture was heated to temperature of 60 0 C for nearly 24-48 hrs. The reaction mixture was filtered and then concentrated and was recrystallized using 70% acetone methanol mixture. NMR was taken in CDCl 3 0.86 (t, 12H), 1.22 (d, 56H), 1.9 (s, 8H), 4.45 (t, 20H), 5.23 (d, 16H), 6.01 (s, 8H), 6.96 (s, 4H). 13 C ( in ppm ) 14.3, 22.9, 28.8, 29.6, 29.9, 30.1, 32.2, 35.0, 39.4, 74.08, 110.0, 113.9, 117.3, 126.1, 133.9, 138.6, 157.1. Synthesis of octaallyloxy resorcinarene (17): 1g of Octahydroxy bromo compound 10 was taken into round-bottomed flask and (20mL/mol) acetone was added to RBF. The reaction mixture was stirred till homogenous mi xture was formed. Then (30eq) potassium carbonate was slowly added over a period of ha lf an hour where the reaction mixture is ice cooled. Here we observe the change in co lor from brown to purple. Then the reaction mixture was brought to room temperature and (30eq) allyl bromide was added. The reaction mixture was heated to temperature of 60 0 C for nearly 24-48 hrs. The reaction mixture was filtered and then concentrated and was recyrstallized using 70% acetone methanol mixture. NMR was taken in CDCl 3 1.45 (t, 12H), 3.5 (s, 4H), 4.2 (s, 14H), 4.57 (m, 16H), 5.04 (dd, 8H), 5.7 (s, 4H). 13 C ( in ppm ) 20.9, 33.9, 74.2, 117.1, 117.6, 125.2, 133.9, 134.1, 138.7, 152.8, 153.9. Synthesis of octaallyloxy resorcinarene (18): 1g of Octahydroxy compound 3 was taken into round-bottomed flask and (20mL/mol) acetone was added to RBF. The reaction mixture was stirred till homogenous mixt ure was formed. Then (30eq) potassium carbonate was slowly added over a period of ha lf an hour where the reaction mixture is ice cooled. Here we observe the change in co lor from brown to purple. Then the reaction mixture was brought to room temperature and (30eq) allyl bromide was added. The 41

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reaction mixture was heated to temperature of 60 0 C for nearly 24-48 hrs. 13 C NMR was taken in CDCl 3. ( in ppm ) 20.96, 32.79, 73.25, 116.12, 123.67, 134.49. Synthesis of octaallyloxy resorcinarene (19): 1g of Octahydroxy compound 4 was taken into round-bottomed flask and (20mL/mol) acetone was added to RBF. The reaction mixture was stirred till homogenous mixt ure was formed. Then (30eq) potassium carbonate was slowly added over a period of ha lf an hour where the reaction mixture is ice cooled. Here we observe the change in co lor from brown to purple. Then the reaction mixture was brought to room temperature and (30eq) allyl bromide was added. The reaction mixture was heated to temperature of 60 0 C for nearly 24-48 hrs. 1 H NMR (CDCl 3 ) ( in ppm ) 0.65 (t, 24H), 1.2 (m, 16H), 1.4 (m, 4H), 4.2 (d, 16H), 4.3 (t, 4H), 5.2 (dd, 16H), 5.9 (m, 8H), 6.2 (s, 4H), 6.9 (s, 4H). Synthesis of octaallyloxy resorcinarene (20): 1g of Octahydroxy compound 5 was taken into round bottomed flask and (20mL/ mol) DMF was added to RBF. The reaction mixture was stirred till homogenous mixture was formed .Then (16eq) potassium tertiary butoxide was slowly added over a period of one hour where the react ion mixture is ice cooled. Here we observe the change in color from brown to purple. Then the reaction mixture was brought to room temperature and (16eq) allyl bromide was added. The reaction mixture is heated to temperature of 70 0 C for nearly 12 hrs. After the reaction is complete the reaction mixture is filtered fr om potassium tertiary butoxide and DMF was distilled over reduced pressure. Dichloromethane was added and reaction was washed with water, then with brine and then c oncentrated and compound was recrystallized in 70% mixture of ethyl acetate and hexa ne. NMR of compound was taken in CDCl 3 42

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( in ppm ) 2.12 (d, J=9.2Hz, 6H), 2.25 ( d, J=9.2Hz, 6H), 3.64 (m, 16H), 5.05-5.20(m, 16H), 5.60 (d, 2H, J=9.6Hz), 6.31 (d, 2H, J=9.6H z), 5.85 (m, 8H), 5.93 (d, 4H), 6.60 (d, 8H, J= 7.6Hz), 6.84 (d, 8H, J= 7.6Hz), 6.86 (s, 4H). Synthesis of octaallyloxy resorcinarene (21): 1g of Octahydroxy compound 6 was taken into round bottomed flask and (20mL/ mol) DMF was added to RBF. The reaction mixture was stirred till homogenous mixture was formed .Then (16eq) potassium tertiary butoxide was slowly added over a period of one hour where the reaction mixture is ice cooled. Here we observe the change in color from brown to purple. Then the reaction mixture was brought to room temperature and (16eq) allyl bromide was added. The reaction mixture is heated to temperature of 70 0 C for nearly 12 hrs. After the reaction is complete the reaction mixture is filtered fr om potassium tertiary butoxide and DMF was distilled over reduced pressure. Dichloromethane was added and reaction was washed with water, then with brine and then c oncentrated and compound was recyrstallized in 70% mixture of ethyl acetate and hexa ne. NMR of compound was taken in CDCl 3 2.12 (d, J=9.2Hz, 6H), 2.25 (d, J=9.2Hz, 6H), 3.64-4.42 (m, 16H), 5.05-5.20 (m, 16H), 5.60 (d, 2H, J=9.6Hz), 6.31 (d, 2H, J=9.6Hz), 5.85 (m, 8H), 5.93 (d, 4H), 6.60 (d, 8H, J= 7.6Hz), 6.84 (d, 4H, J= 7.6Hz), 6.86 (s, 4H). Synthesis of octaallyloxy resorcinarene (22): 1g of Octahydroxy compound 7 was taken into round bottomed flask and (20mL/mol) DMF was added to RBF. The reaction mixture was stirred till homogenous mixture was formed .Then (16eq) potassium tertiary butoxide was slowly added over a period of one hour where the reaction mixture is ice cooled. Here we observe the change in color from brown to purple. Then the reaction mixture was brought to room temperature and (16eq) allyl bromide was added. The 43

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reaction mixture is heated to temperature of 70 0 C for nearly 12 hrs. After the reaction is complete the reaction mixture is filtered fr om potassium tertiary butoxide and DMF was distilled over reduced pressure. Dichloromethane was added and reaction was washed with water, then with brine and then c oncentrated and compound was recyrstallized in 70% mixture of ethyl acetate and hexa ne. NMR of compound was taken in CDCl 3 Synthesis of octaallyloxy resorcinarene (23): 1g of Octahydroxy compound 8 was taken into round bottomed flask and (20mL/ mol) DMF was added to RBF. The reaction mixture was stirred till homogenous mixture was formed .Then (16eq) potassium tertiary butoxide was slowly added over a period of one hour where the react ion mixture is ice cooled. Here we observe the change in color from brown to purple. Then the reaction mixture was brought to room temperature and (16eq) allyl bromide was added. The reaction mixture is heated to temperature of 70 0 C for nearly 12 hrs. After the reaction is complete the reaction mixture is filtered fr om potassium tertiary butoxide and DMF was distilled over reduced pressure. Dichloromethane was added and reaction was washed with water, then with brine and then c oncentrated and compound was recyrstallized in 70% mixture of ethyl acetate and hexa ne. NMR of compound was taken in CDCl 3 Synthesis of bridged resorcinarene (24) : To a stirred solution of octa-allyloxy methyl resorcinarene (13) (1gm, .877 mmole) in dry methylen e chloride (90mL) was added Grubbs catalyst (5 mole%, 0.034gm, 0.042 mmole) in dry methylene chloride (25mL) at room temperature. Reaction was continued for 4days. Reaction mixture was then concentrated using a rotary evaporator and compound was obtained by column chromatography. 44

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Synthesis of bridged resorcinarene (25) : To a stirred solution of octa-allyloxy methyl resorcinarene (18) (1gm, .877 mmole) in dry methylen e chloride (90mL) was added Grubbs catalyst (5 mole%, 0.034gm, 0.042 mmole) in dry methylene chloride (25mL) at room temperature. Reaction was continued for 4days. Reaction mixture was then concentrated over rotary evaporat or and was separated by column. Synthesis of bridged-resorcinarene (26) : To a stirred solution of octa-allyloxy-phenylresorcinarene ( 22) (1gm, 0.89 mmole) in dry methylen e chloride (93mL) was added grubbs catalyst (8 mole%, 0.058gm, 0.071 mmole) in dry methylene chloride (20mL) at room temperature. Reaction was continued for 4days. Reaction mixture was then concentrated over rotavapor and column chromatography was run using 10% ethyl acetate and 90% hexane solvent system to sepa rate two spots. Second spot (fraction) showed that four allyl groups are closed forming two bridges. It was confirmed by 13 C, DEPT, Mass spectroscopy. DEPT (CDCl 3 ) in ppm 41.8, 63.8, 68.6, 96.2, 98.99, 115.3, 124.3, 126.6, 126.8, 127.3, 127.9, 128.1, 132.1, 132.7; MALDI m/z 1057.785 (M + + H), 1079.814 (M + + Na). Synthesis of bridged-resorcinarene (27) : To a stirred solution of octa-allyloxybromophenyl-resorcinarene (23) (1gm, 0.89 mmole) in dry me thylene chloride (93mL) was added grubbs catalyst (8 mole%, 0.058gm, 0.071 mmole) in dry methylene chloride (20mL) at room temperature. Reaction was continued for 4days. Reaction mixture was then concentrated over rota vapor and column chromatogr aphy was run using 10% ethyl acetate and 90% hexane solvent system to sepa rate two spots. Second spot (fraction) showed that four allyl groups are closed forming two bridges. It was confirmed by 13 C, DEPT, Mass spectroscopy. DEPT (CDCl 3 ) in ppm 41.8, 63.8, 68.6, 96.2, 98.99, 115.3, 45

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124.3, 126.6, 126.8, 127.3, 127.9, 128.1, 132.1, 132.7; MALDI m/z 1057.785 (M + + H), 1079.814 (M + + Na). Synthesis of bridged-resorcinarene (28) : To a stirred solution of octa-allyloxyphenyl-methylresorcinarene ( 20) (1gm, 0.82 mmole) in dry me thylene chloride (86mL) was added grubbs catalyst (8 mole%, 0.054gm, 0.066 mmole) in dry methylene chloride (19mL) at room temperature. Reaction was continued for 4days. Reaction mixture was then concentrated over rota vapor and column chromatogr aphy was run using 10% ethyl acetate and 90% hexane solvent system to sepa rate two spots. Second spot (fraction) showed that two allyl groups are closed forming one bridge. It was confirmed by 13 C, DEPT, Mass spectroscopy. 13 C NMR (CDCl 3 ) in ppm (10.8, 10.9, 11.1, 11.3), 24.9, 36.8, (44.2, 44.7, 44.9, 45.0), (68.6, 71.0, 73.9, 74.2), (116.4, 116.6, 116.6, 116.8, 117.0, 117.3), (123.8, 124.1, 125.3, 125.8, 125.9, 126.3, 127.4, 127.4, 127.8, 127.8, 128.3, 129.0, 129.2, 130.1, 131.2, 132.2, 132.4, 132.5, 132.7, 132.82, 132.8, 133.1, 133.2), (134.1, 134.1, 134.2, 134.2, 134.3, 134.3, 134.4), (141.4, 143.4, 143.6, 144.0), (154.1, 154.3, 154.8, 154.9, 155.0, 155.0, 155.1, 155.6). Synthesis of bridged-resorcinarene (29) : To a stirred solution of octa-allyloxybromophenyl-methylresorcinarene (21) (1gm, 0.67 mmole) in dry methylene chloride (70mL) was added grubbs catalyst (8 mole %, 0.044gm, 0.054 mmole) in dry methylene chloride (15mL) at room temperature. Reaction was continued for 4days. Reaction mixture was then concentrated over rotavapor and column chromatography was run using 10% ethyl acetate and 90% hexane solvent sy stem to separate two spots. Second spot (fraction) showed that two allyl groups are closed forming one bridge. It was confirmed by 13 C, DEPT, Mass spectroscopy. 13 C NMR (CDCl 3 ) in ppm 10.9, 11.0, 11.2, 11.3, 46

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14.4, 29.9, 43.7, 44.1, 44.3, 44.5, 69.2, 73.8, 74.2, 74.5, 110.0, 116.6, 116.8, 116.9, 117.3, 117.5, 117.8, 120.0, 120.1, 120.1, 124.3, 124.7, 125.8, 126.4, 126.8, 128.2, 129.7, 130.6, 130.7, 130.8, 130.9, 130.9, 131.0, 132.3, 132.4, 132.5, 132.6, 133.8, 134.0, 134.1, 134.2, 140.5, 142.6, 142.9, 143.6, 154.3, 154.8, 155.0, 155.2, 155.3, 155.4, 155.9. Synthesis of bridged resorcinarene (30) : To a stirred soluti on of octa-allyloxy bromo heptyl resorcinarene (15) (1gm, .684 mmole) in dry me thylene chloride (72mL) was added Grubbs catalyst (5 mole%, 0.028gm, 0.034 mmole) in dry methylene chloride (25mL) at room temperature. Reaction was continued for 4days. Reaction mixture was then concentrated over Rota vapor and was precipitated from mixture of acetone and dichloromethane. 1 H NMR 0.86 (t, 12H), 1.23 (d, 56H), 1.9 (s, 8H), 4.82 (t, 20H), 5.95 (s, 8H), 6.96 (s, 4H). 13 C NMR 14.3, 22.9, 27.8, 29.6, 29.8, 29.9, 32.2, 36.6, 37.7, 77.5, 109.9, 113.6, 125.3, 130.1, 135.3, 154.2. Synthesis of bridged resorcinarene (31) : To a stirred soluti on of octa-allyloxy bromo decyl resorcinarene (16) (1gm, .614 mmole) in dry methyl ene chloride (65mL) was added Grubbs catalyst [8 mole%, 0.025gm, 0.031 mmole] in dry methylene chloride (25mL) at room temperature. Reaction was continued for 4days. Reaction mixture was then concentrated over Rota vapor and was recrys tallised from mixture of ethyl acetate and hexane. 1 H NMR ( CDCl 3 ) 0.86 (t, 12H), 1.22 (d, 56H), 1.9 (s, 8H), 4.8 ( d, 12H), 6.01 (s, 8H), 6.96 (s, 4H). 13 C NMR 14.3, 22.9, 28.8, 29.6, 29.9, 30.1, 32.2, 35.0, 39.4, 74.08, 110.0, 113.9, 126.1, 133.9, 138.6, 157.1. 47

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Synthesis of bridged resorcinarene (32) : To a stirred soluti on of octa-allyloxy bromo methyl resorcinarene (17) (1gm, .877 mmole) in dry me thylene chloride (90mL) was added Grubbs catalyst (5 mole%, 0.034gm, 0.042 mmole) in dry methylene chloride (25mL) at room temperature. Reaction was continued for 4days. Reaction mixture was then concentrated over Rota vapor and was precipitated from mixture of acetone and dichloromethane. NMR was taken in CDCl 3 .( ppm ) 20.9, 33.9, 74.3, 117.1, 117.3, 125.0, 134.1, 139.5, 153.9. Synthesis of Ethyl ester of 2,4 di methoxy Cinnamic acid (33):0.3g of 2,4 dimethoxy cinnamic acid was taken into RBF and 14 ml of acetone(10mL/mmol) was added and stirred still homogenous solution was obtained. To this solution 1g (5eg) of potassium carbonate was added in portion wi se and 0.3mL (2eq) of ethyl iodide was added and the reaction was refluxed for 12 hrs. It was allo wed to cool and base was filtered off, concentrated in vacuum, and so obtained product was taken for NMR. 1 H NMR revealed the existence of compound. Following peaks were found in CDCl 3 1.30 (t, J=7.25) 3.83 (d, J=7.5) 4.23 (q, J= 7) 6.40 (s), 6.45 (m), 6.48 (m), 7.42 (d ,J= 8.75) 7.94 ( d, J= 16.25). Synthesis of C-Ethyl Dime thoxy resorcinarene (34):1g of compound 33 was taken into RBF and 6.5mL of chloroform (5mL/mmol) was added to the compound and allowed to stir for 5 min. 0.26mL of BF 3 etherate (0.2mL/mmol) was added to the reaction mixture and the continued for 10hrs.The reaction wa s monitored by TLC and after 10hrs the reaction was quenched with methanol and so ob tained precipitate was filtered off and it was concentrated in vacuum. The reaction mixture was purified by column chromatography (5% methanol and dichloromethane) and NMR was taken in CDCl 3 48

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1.01 ( d, J= 9Hz), 1.13 ( m), 2.87 (d, J= 7.75H z), 3.72 ( q, J=4.75Hz), 4.86(s), 6.19 ( d, J= 9.75Hz), 6.54(s). Synthesis of demethylated Resorcinarene (35):1g of compound 34 was taken into RBF and 40mL of dichloromethane was added to the reaction mixture. The reaction mixture was cooled in ice bath for 15 min and 2.8g of aluminium trichloride (20eq) was added in portion wise and reaction was allowed to continue for 12 hrs. The reaction was monitored by TLC. The reaction mixture was quenched with water and extracted into Dichloromethane and concentrated in vacuum. The major lower Rf s pot was separated by column chromatography and NMR was taken in DMSO d 6 1.01 (d, J= 9Hz), 1.13 ( m), 2.87 (d, J= 7.75Hz), 3.72 (q, J=4.75Hz), 4.86 (s ), 6.19 ( d, J= 9.75hz), 6.54 (s) 8.8 (m). Synthesis of Hydroxy ethyl Resorcinarene (36):0.5g of compound 34 was taken into RBF and 16mL of tetrahydrofuran was added to the reaction mixture. The reaction mixture was cooled in ice bath for 15 min and 80mg of Lithium aluminium hydride (4 eq) was added in portion wise and reaction was allowed to conti nue for 12 hrs. The reaction was monitored by TLC and quenched with 0.5mL of water followed by 0.5 mL of saturated sodium chloride solu tion and extracted into ethyl acet ate. It was concentrated in vacuum. The major lower Rf spot was separated by column chromatography and NMR was taken in CDCl 3 1.13 ( m), 2.01 (s) 2.87 (d, J= 7.75Hz), 4.86 (s), 6.19 ( d, J= 9.75hz), 6.54 (s). 49

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4.2 Crystal data of Resorcinarenes (1) Crystal data of allyloxy -resorcinarene (13): Colorless parallelepiped, C 60 H 72 O 8 F.W= 921.18, triclinic, space group P1, a= 12.066(10), b= 15.927(12), c= 20.122(15) A 0 = 84.594(16) 0 V= 3368(5) A 0 3 Z= 2, D = 1.129 Mg m -3 T= 115 K. Data were collecte d on Kappa CCD diffractometer (2.5 0 < < 29.5 0 ) using Mo K radiation, ( = 0.71073A 0 ). From the 80902 reflections measured, 11348 (I > 2 (I)) were used in the refinements. (2) Crystal data of allyloxy -resorcinarene (15): Colorless fragment, C 56 H 56 O 8 Br 4 F.W.= 1176.65, orthorhomb ic, space group P2, a= 8.826(17), b= 19.85(4) c= 29.78(4) A 0 = 90 0 V= 5217.6(17) A 0 3 Z= 4, D = 1.185 Mg m -3 T= 110 K. Data were collected on Kappa CCD diffractometer (2.5 0 < < 29.5 0 ) using Mo K radiation, ( = 0.71073A 0 ). From the 9131 reflections measured, 6563 (I > 2 (I)) were used in the refinements. (3) Crystal data of allyloxy -resorcinarene (16): Colorless fragment, C 88 H 124 O 8 Br 4 F.W.= 1629.51, monoclinic, space group P2(1), a= 27.061(3), b= 18.98(18), c= 16.289(13) A 0 = 90.746(2) 0 V= 8366.2(13) A 0 3 Z= 4, D = 1.294 Mg m -3 T= 100 K. Data were collected on Kappa CCD diffractometer (2.5 0 < < 29.5 0 ) using Mo K radiation, ( = 0.71073A 0 ). From the 40537 reflections measured, (I > 2 (I)) were used in the refinements. (4) Crystal data of allyloxy-resorcinarene (21): Colorless fragment, C 80 H 80 O 8 Br 4 F.W= 1529.44, triclinic, space group P1, a= 12.36(2), b= 13.691(3), c= 19.796(4) A 0 92.301(11) 0 V= 3189(11) A 0 3 Z= 2, D = 1.218 Mg m 3 T= 110 K. Data were collected on Kappa CCD diffractometer (2.5 0 < < 29.5 0 ) using 50

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Mo K radiation, ( = 0.71073A 0 ). From the 9131 reflections measured, 6984 (I > 2 (I)) were used in the refinements. 51

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REFERENCES 1) (a) .Hgberg, A.G.S.; J.Am.Chem.Soc. 102 ( 1980), 6046. (b) Hgberg, A.G.S,; J. Org. Chem. 45 ( 1980), 4498. (c) For a general review see:. T immerman ,P;. Verboom ,W.; Reinhoudt, D.N.; Tetrahedron 52 ( 1996), 2663. 2), Enrique, B;, Eric, D. S.; Buchhol z, B,; Ballester, J,P;. Javier d M,; An-gew Chem Int Ed ( 2007), 46, 198-201. 3 (a) Cram ,D.J.; and. Cram, J.M,; Containe r Molecules and Their Guests, Royal Society of Chemistry, Cambridge ( 1994). (b) Cram ,D.J, Nature 356 ( 1992), 29. (c) Asfari ,: Z,;. Bhmer ,V.;. Harrowfield ,J .;and. Vicens, J.;, Calixarenes 2001, Kluwer Academic, Dordrecht ( 2001). (d) Gutsche C.D..; Editor, Calixarenes Revisited The Royal Society of Chemistry, London ( 1998). (e) Bhmer .;V, Angew. Chem., Int. Ed. Engl. 34 ( 1995), 713 (f) Jasat, A and. Sherman ,J.C.; Chem. Rev. 99 ( 1999), 931 4) (a) Aoyama, Y,;. Tanaka, Y.; and. Sugahara, S.; J. Am. Chem. Soc. 111 ( 1989),. 5397. (b) Aoyama, Y.; Nonaka ,Y.;. Tana ka ,Y.;. Toi ,H .;and. Ogoshi ,H.; J. Chem. Soc., Perkin Trans. 2 ( 1989), 1025 52

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(c) Aoyama ,Y.; Tanaka ,Y..;. Toi ,H.; and. Ogoshi,H.; J. Am. Chem. Soc. 110 ( 1988), 634 (d) Schneider, H.;. Guttes, D.; and. Schneider, U.; Angew. Chem., Int. Ed. Engl. 25 ( 1986), 647 (e) Van-Velzen,E.U.T.;. Engbersen ,J.F.J.; Delagne, P.J.;. Mahy, J.W.; and. Reinhoudt D.N. J. Am. Chem. Soc. 117 ( 1995), 6853. (f) Laughrey ,Z.R.;. Gibb ,C.L .D.;. Senechal,T.;and. Gibb,B.C.; Chem. Eur. J. 9 ( 2003), 130. 5) (a) Heinz, T.;. Rudkevich ,D.M.; and. Rebek ,J Jr..; Nature 394 ( 1998), 764. (b) Shivanyuk,A.; and. Rebek, J Jr.; Proc. Natl. Acad. Sci. U.S.A. 98 ( 2001), 7762. (c) Shivanyuk, A.; and. Rebek ,J Jr..; Chem. Commun. ( 2001), 2424 (d) Shivanyuk ,A.; and. Rebek ,J Jr..; J. Am. Chem. Soc. 125 ( 2003), 3432. (e) Gerkensmeier, T.;. Iwanek,W.;. Agena, C.;. Frhlich ,R.;. Kotila ,S.;. Nther, C.; and. Mattay ,J.; Eur. J. Org. Chem. ( 1999), 2257 (f) .MacGillivray, L.R.; and Atwood,J.L.; Nature 389 ( 1997), 469. (g) Antesberger, J.;. Cave ,G.W.V.;. Fe rrarelli ,M.C.;. Heaven, M.W.;. Raston, C.L.; and. Atwood, J.L.; Chem. Commun. ( 2005), 892 (h) Atwood ,J.L.;. Barbour ,L.J.; and. Jerga ,A.; Chem. Commun. ( 2001), 2376. (i) Avram, L.; and Cohen ,Y.; Org. Lett. 18 ( 2003), 3329. (j) Avram,L.; and. Cohen, Y.; J. Am. Chem. Soc. 125 ( 2003), 16180. (k) Avram, L.; and. Cohen, Y.; J. Am. Chem. Soc. 126 ( 2004 ), 11556 6) (a)Cram, D J.; Cram, J M.; Editors. Container Molecules and Their Guests. ( 1997) 53

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(b) Asfari, Z; B, Volker, H, J; Vicens, J; Editors. Calixarenes 2001 7) (a) Rebek, J, Jr..; Acc. Chem. Res. (1999), 32(4), 278-286. (b) Fujita, M; Fujita, N; Ogura, K; Yamaguchill, K. Nature (London) ( 1999) 400(6739), 52-55. (c). Danny F. O.;, James, C.;, Emma,Wilkinson.;.; Drew,J. S.; Michael G. B.; MacLean, E J.; Teat, S J.; Beer, P D..; J. Am. Chem. Soc. ( 2006), 128(21), 6990-7002. 8), Oliver,H.; Alexander, S. ;, Markus,J.;, Arne, Luetzen.; Synthesis ( 2006 ), (3), 519-527. 9) Baeyer, A. Ber. Disch. Chem. Ges. 1872, 5, 25. 10) Michael, A. J. Am. Chem. Soc 1883, 5, 338. 11) Niederl, J. B.; Vogel, H. J. J. Am. Chem. Soc. 1940, 62, 2512. 12) a)Erdtman, H.; Hogberg, S.; Abrahamsson, S.; Nilsson, Bo. Tetrahedron Letters ( 1968), (14), 1679-82. b)Middel, O.; Verboom, W.; Hulst, R.; Kooijman, H.; Spek, A. L.; Reinhoudt, D. N J. Org. Chem. 1998, 63, 8259. 13) Tunstad, L. M.; Tucker, J. A.; Dalcanale, E.; Weiser, J.; Bryant, J. A.; Sherman, J. C.; Helgeson, R. C.; Knobler, C. B.; Cram, D. J. J. Org. Chem. 1989, 54, 1305. 14) (a) Cram, D J.; Choi, H J.; Bryant, J A.; Knobler, C.; J. Am. Chem. Soc ( 1992) 114(20), 7748-65. (b) Sherman, J. C. Tetrahedron 1995, 51, 3395. 15) Aakeroy, C B.; Schultheiss, N; Desper, J.; Cryst.Eng.Comm ( 2006), 8(7), 502-506. 16) (a) Roman, E.; Chas, M.; Quintela ,M.;; Peinador,J.;; Kaifer,Carlos.; Angel E. Tetrahedron ( 2002), 58(4), 699-709. 54

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17) a) Berkeley,SJ.; Timothy G,E.; Org. Lett ( 2001), 3(4), 577-579. b), Bruno ,B.; Di Giovanni, Cristina ,M,; Monache, Delle.; Gi uliano; D R.; Cristina ,M.;, Eszter, G-B.;, Maurizio, B.;, Federico ,C.; Andrea, T.; Antonello ,S.; J. Org. Chem. ( 1994), 59(6), 1532-41. 18) (a) Pitarch, M.; Mckee, V.; Nieuwenhuyzen, M.; McKervey, M. A. J. Org. Chem. 1998, 63, 946. (b) Zuercher, W. J.; Hashimoo, M.; Grubbs, R. H. J. Am. Chem. Soc. 1996, 118, 6634. (c) McKervey, M. A.; Pitarch, M. Chem. Commun. 1996 1689. 19) Chen, C. F.; Lu, L. G.; Hu, Z. Q.; Peng, X. X.; Huang, Z. T. Tetrahedron 2005, 61, 3853. 20) Balasubramanian, R.; Kwon, Y-G.;, Alexander,W.; J. Mat. Chem (2007 ), 17(1), 105112. 21) Lamartine, R.; Tsukada, M.; Wilson, D.; Shirata, A.;. Comptes Rendus Chimie (2002), 5(3), 163-169. 55

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APPENDICES ( Spectra of Compounds) 56

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Figure 14. 1 H NMR of compound 1 CH3 CH3 H3C CH3 CH3 CH3 HO OH OH HO HO HO OH OH H3C H3C CH3 CH3 H3C CH3 CH3 CH3 HO OH OH HO HO HO OH OH H3C H3C Figure 15. 13 C NMR of compound 1. 57

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C6H13 C6H13 H3C CH3 CH3 CH3 HO OH OH HO HO HO OH OH C6H13 C6H13 Figure 16. 1 H NMR of compound 2 C6H13 C6H13 H3C CH3 CH3 CH3 HO OH OH HO HO HO OH OH C6H13 C6H13 Figure 17. 13 C NMR of compound 2 58

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CH3 CH3 HO OH OH HO HO HO OH OH H3C H3C Figure 18. 1 H NMR of compound 3 CH3 CH3 HO OH OH HO HO HO OH OH H3C H3C Figure 19. 13 C NMR of compound 3 59

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Figure 20. 1 H NMR of compound 4 CARBON 150 140 130 120 110 100 90 80 70 60 50 40 30 20 Chemical Shift (ppm) 0 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09 0.10 Normalized Intensity 152.36 123.70 52.50 40.80 40.63 40.54 40.47 40.37 40.30 40.21 40.04 39.87 34.22 32.14 29.57 28.44 23.02 22.85 22.64 14.84 14.58 C6H13 C6H13 HO OH OH HO HO HO OH OH C6H13 C6H13 C6H13 C6H13 HO OH OH HO HO HO OH OH C6H13 C6H13 Figure 21. 13 C NMR of compound 4 60

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Ph Ph HO OH OH HO HO HO OH OH Ph Ph H3C CH3 CH 3 H3C Figure 22. 1 H NMR of compound 5 Ph Ph HO OH OH HO HO HO OH OH Ph Ph H3C CH3 CH 3 H3C Figure 23. 13 C NMR of compound 5 61

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PhBr PhBr HO OH OH HO HO HO OH OH BrPh BrPh H3C CH3 CH 3 H3C Figure 24. 1 H NMR of compound 6 PhBr PhBr HO OH OH HO HO HO OH OH BrPh BrPh H3C CH3 CH 3 H3C Figure 25. 13 C NMR of compound 6 62

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P ROTON 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 Chemical Shift (ppm) 0 0.005 0.010 0.015 0.020 0.025 0.030 0.035 0.040 0.045 0.050 0.055 0.060 Normalized Intensity 2.39 3.26 3.30 3.31 3.36 5.52 6.01 6.63 6.83 8.46 Ph Ph HO OH OH HO HO HO OH OH Ph Ph Figure 26. 1 H NMR of compound 7 resorcinol-benzaldehyde-hydroxy 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 Chemical Shift (ppm) 0 0.05 0.10 0.15 0.20 0.25 0.30 0.35 Normalized Intensity 146.06 129.16 127.94 125.43 42.02 40.20 40.11 39.94 39.77 39.61 39.44 39.27 39.10 Ph Ph HO OH OH HO HO HO OH OH Ph Ph Figure 27. 13 C NMR of compound 7 63

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Figure 28. 1 H NMR of compound 8 PhBr PhBr HO OH OH HO HO HO OH OH BrPh BrPh PhBr PhBr HO OH OH HO HO HO OH OH BrPh BrPh Figure 29. 13 C NMR of compound 8 64

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CH3 CH3 Br B r Br B r HO OH OH HO HO HO OH OH H3C H3C Figure 30. 1 H NMR of compound 10 CH3 CH3 Br Br Br Br HO OH OH HO HO HO OH OH H3C H3C Figure 31. 13 C NMR of compound 10 65

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C6H13 C6H13 Br B r Br B r HO OH OH HO HO HO OH OH C6H13 C6H13 Figure 32. 1 H NMR of compound 11 CARBON 180 160 140 120 100 80 60 40 20 Chemical Shift (ppm) 0 0.05 0.10 0.15 0.20 0.25 0.30 Normalized Intensity 180.08 149.28 126.15 101.98 40.81 40.72 40.64 40.55 40.39 40.22 40.05 39.89 39.72 32.13 30.22 29.44 28.36 22.80 14.56 C6H13 C6H13 Br B r Br B r HO OH OH HO HO HO OH OH C6H13 C6H13 Figure 33. 13 C NMR of compound 11 66

PAGE 81

C9H19 C9H19 Br B r Br B r HO OH OH HO HO HO OH OH C9H19 C9H19 Figure 34. 1 H NMR of compound 12 sumedhdecylhydroxyc13 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Chemical Shift (ppm) 0.005 0.010 0.015 0.020 0.025 0.030 0.035 Normalized Intensity 149.32 125.97 101.94 40.71 40.62 40.54 40.45 40.29 40.12 39.95 39.79 39.62 32.09 32.03 30.18 29.39 28.37 22.80 14.65 14.58 C9H19 C9H19 Br B r Br B r HO OH OH HO HO HO OH OH C9H19 C9H19 Figure 35. 13 C NMR of compound 12 67

PAGE 82

Figure 36. 1 H NMR of compound 13 CARBON 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Chemical Shift (ppm) 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Normalized Intensity 134.69 123.87 116.33 77.57 77.26 76.94 33.00 21.17 10.72 PROTON 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 Chemical Shift (ppm) 0.05 0.10 0.15 0.20 0.25 0.30 0.35 0.40 0.45 0.50 0.55 0.60 0.65 0.70 Normalized Intensity 7.19 6.07 5.74 5.46 5.18 5.01 4.51 4.49 4.48 4.46 2.24 2.10 1.85 1.50 1.45 1.43 CH3 CH3 O O O O O O O O H3C H3C H3C CH3 CH3 H3C CH3 CH3 O O O O O O O O H3C H3C H3C CH3 CH3 H3C Figure 37. 13 C NMR of compound 13 68

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C6H13 C6H13 O O O O O O O O C6H13 C6H13 H3C CH3 CH3 H3C Figure 38. 1 H NMR of compound 14 C6H13 C6H13 O O O O O O O O C6H13 C6H13 H3C CH3 CH3 H3C Figure 39. 13 C NMR of compound 14 69

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C6H13 C6H13 Br Br Br Br O O O O O O O O C6H13 C6H13 Figure 40. 1 H NMR of compound 15 C6H13 C6H13 Br Br Br Br O O O O O O O O C6H13 C6H13 Figure 41. 13 C NMR of compound 15 70

PAGE 85

Figure 42. 1 H NMR of compound 16 C9H19 C9H19 Br Br Br O O O O O O O O C9H19 C9H19 Br Figure 43. DEPT NMR of compound 16 71

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CH3 CH3 Br Br Br Br O O O O O O O O H3C H3C Figure 44. 1 H NMR of compound 17 CH3 CH3 Br Br Br Br O O O O O O O O H3C H3C Figure 45. 13 C NMR of compound 17 72

PAGE 87

CH3 CH3 O O O O O O O O H3C H3C Figure 46. DEPT NMR of compound 18 C6H13 C6H13 O O O O O O O O C6H13 C6H13 Figure 47. 1 H NMR of compound 19 73

PAGE 88

Figure 48. 13 C NMR of compound 19 Ph Ph O O O O O O O O Ph Ph H3C CH3 CH3 H3C Figure 49. 1 H NMR of compound 20 74

PAGE 89

Ph Ph O O O O O O O O Ph Ph H3C CH3 CH3 H3C Figure 50. 13 C NMR of compound 20 PhBr PhBr O O O O O O O O BrPh BrPh H3C CH3 CH3 H3C Figure 51. 1 H NMR of compound 21 75

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PhBr PhBr O O O O O O O O BrPh BrPh H3C CH3 CH3 H3C Figure 52. 13 CNMR of compound 21 Ph Ph O O O O O O O O Ph Ph Figure 53. 1 H NMR of compound 22 76

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Figure 54. 1 H NMR of compound 23 PhBr PhBr O O O O O O O O BrPh BrPh Figure 55. 13 C NMR of compound 26 Ph Ph R1 H H O O O O O O O O Ph Ph 77

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Ph Ph H3C CH3 CH3 O O O O O O O O Ph Ph Figure 56. 1 H NMR of compound 28 Figure 57. 1 H NMR of compound 29 PhBr PhBr H3C CH3 CH3 CH3 O O O O O O O O BrPh BrPh 78

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C6H13 C6H13 Br Br Br O O O O O O O O C6H13 C6H13 Figure 58. 1 H NMR of compound 30 C9H19 C9H19 Br Br Br Br O O O O O O O O C9H19 C9H19 Figure 59. 1 H NMR of compound 31 79

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sp-d-113rcm 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 Chemical Shift (ppm) 0 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09 0.10 0.11 0.12 Normalized Intensity 134.14 77.53 77.27 77.02 37.74 36.62 32.18 29.96 29.83 29.57 27.80 22.94 22.89 14.41 14.37 14.29 1.27 C9H19 C9H19 Br Br Br Br O O O O O O O O C9H19 C9H19 Figure 60. 13 C NMR of compound 31 OMe MeO O O Figure 61. 1 H NMR of compound 33 80

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CH2COOEt EtOOCH2C EtOOCH2C CH2COOEt OMe OMe OMe MeO MeO MeO M e O OMe Figure 62. 1 H NMR of compound 34 CH2COOEt EtOOCH2C EtOOCH2C CH2COOEt OH OMe OH HO MeO MeO M e O OMe Figure 63. 1 H NMR of compound 35 81

PAGE 96

CH2CH2OH HOH2CH2C HOH2CH2C CH2CH2OH OMe OMe OMe MeO MeO MeO M e O OMe Figure 64. 1 H NMR of compound 36 82


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Muppalla, Kirankirti.
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Functionalization of resorcinarenes and study of antimicrobial activity
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by Kirankirti Muppalla.
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[Tampa, Fla.] :
b University of South Florida,
2007.
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ABSTRACT: Cavitands are very important class of compounds in supramolecular chemistry. These molecules contain rigid enforced cavity,and have attracted considerable attention in supramolecular chemistry as building blocks for the construction of carcerands, hemicarcerands, and other host guests complexes. Nearly 40 years ago, Niederl and Vogel laid foundation for the study of such type of condensation reactions. In our laboratory we are involved in synthesis of resorcinarenes with readily available substrates such as resorcinol and aldehydes to form a cyclic tetramer. Herein, I present detailed studies about the functionalization of the synthesized tetramers and their antimicrobial activity. Octahydroxy resorcinarenes were synthesized and perallylated which served as acyclic diene precursors for ring closing metathesis reaction. Studies were carried out to see effect of C-2 substituent of resorcinol and effect of aryl substituents, and aliphatic substituents on ring closing metathesis. This thesis describes the synthesis of bridged resorcinarenes and study of antimicrobial activity of resorcinarenes.
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Thesis (M.S.)--University of South Florida, 2007.
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Includes bibliographical references.
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Text (Electronic thesis) in PDF format.
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Advisor: Kirpal S Bisht, Ph.D.
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NMR.
Crystal structure.
Antimicrobial activity.
Cavitand.
Ring closing metathesis.
Resorcinarene.
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Dissertations, Academic
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Masters.
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t USF Electronic Theses and Dissertations.
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